2022/05/13 更新

写真a

ダンサコ ヒロミチ
團迫 浩方
DANSAKO Hiromichi
所属
医歯薬学域 准教授
職名
准教授
外部リンク

学位

  • 博士(医学) ( 2004年9月   岡山大学 )

  • 学士(農学) ( 1993年3月   佐賀大学 )

研究キーワード

  • ミトコンドリア機能不全

  • 自然免疫機構

  • 細胞外小胞

  • C型肝炎ウイルス(HCV)

  • B型肝炎ウイルス(HBV)

研究分野

  • ライフサイエンス / ウイルス学

  • ライフサイエンス / 細胞生物学

経歴

  • 岡山大学大学院医歯薬学総合研究科   腫瘍微小環境学(旧 腫瘍ウイルス学)   准教授

    2021年5月 - 現在

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  • 岡山大学大学院医歯薬学総合研究科   腫瘍ウイルス学分野   准教授

    2016年4月 - 2021年4月

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  • 岡山大学大学院医歯薬学総合研究科   腫瘍ウイルス学分野(旧 分子生物学分野)   助教

    2007年4月 - 2016年3月

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  • 岡山大学大学院医歯薬学総合研究科   分子生物学分野   助教

    2005年4月 - 2007年3月

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  • 岡山大学大学院医歯学総合研究科   分子生物学分野   助手

    2004年4月 - 2005年3月

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  • 岡山大学   医学部第二内科   技官

    1997年4月 - 2004年3月

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▼全件表示

所属学協会

 

論文

  • Extracellular vesicles activate ATM‐Chk2 signaling pathway through the intercellular transfer of mitochondrial DNA in HBV‐infected human hepatocytes 査読

    Hiromichi Dansako, Youki Ueda, Shinya Satoh, Nobuyuki Kato

    The FASEB Journal   35 ( 6 )   2021年6月

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    担当区分:筆頭著者, 責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1096/fj.202002678r

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1096/fj.202002678R

  • Identification of ribavirin-responsive cis-elements for GPAM suppression in the GPAM genome. 国際誌

    Daichi Onomura, Shinya Satoh, Youki Ueda, Hiromichi Dansako, Nobuyuki Kato

    Biochemical and biophysical research communications   533 ( 1 )   148 - 154   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Glycerol-3-phosphate acyltransferase, mitochondrial (GPAM) is a rate-limiting enzyme catalyzing triglyceride synthesis. Recently, we demonstrated that the anti-viral drug ribavirin (RBV) reduces GPAM expression by downregulating CCAAT/enhancer-binding protein α (C/EBPα). However, the precise mechanisms of GPAM suppression have remained unclear. Here, we found that RBV suppressed GPAM expression by downregulating not only C/EBPα, but also sterol regulatory element-binding protein-1c (SREBP-1c). We also found that cis-elements regulated by C/EBPα and SREBP-1c functioned as distal and proximal enhancers, respectively, to express hepatocyte- and adipocytes-specific GPAM variants. These results imply that RBV disrupts formation of the enhancer machineries on the GPAM genome by downregulating both transcription factors. Our findings may contribute to the development of treatments for fatty liver diseases caused by aberrant triglyceride synthesis.

    DOI: 10.1016/j.bbrc.2020.08.112

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  • Study of multiple genetic variations caused by persistent hepatitis C virus replication in long-term cell culture. 査読 国際誌

    Nobuyuki Kato, Youki Ueda, Hiroe Sejima, Weilin Gu, Shinya Satoh, Hiromichi Dansako, Masanori Ikeda, Kunitada Shimotohno

    Archives of virology   165 ( 2 )   331 - 343   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The most characteristic feature of the hepatitis C virus (HCV) genome in patients with chronic hepatitis C is its remarkable variability and diversity. To better understand this feature, we performed genetic analysis of HCV replicons recovered from two human hepatoma HuH-7-derived cell lines after 1, 3, 5, 7, and 9 years in culture: The cell lines 50-1 and sO harbored HCV 1B-1 and O strain-derived HCV replicons established in 2002 and 2003, respectively. The results revealed that genetic variations in both replicons accumulated in a time-dependent manner at a constant rate despite the maintenance of moderate diversity (less than 1.8% difference) between the clones and that the mutation rate in the 50-1 and sO replicons was 2.5 and 2.9 × 10-3 base substitutions/site/year, respectively. We found that the genetic distance of both replicons increased from 7.9% to 10.5% after 9 years in culture. In addition, we observed that the guanine + cytosine (GC) content of both replicon RNAs increased in a time-dependent manner, as observed in our previous studies. Finally, we demonstrated that the high sensitivity of both replicons to direct-acting antivirals was maintained even after 9 years in culture. Our results suggest that long-term cultured HCV replicon-harboring cells are a useful model for understanding the variability and diversity of the HCV genome and the drug sensitivity of HCV in patients with chronic hepatitis C.

    DOI: 10.1007/s00705-019-04461-0

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  • A new hepatoma cell line exhibiting high susceptibility to hepatitis B virus infection. 査読 国際誌

    Youki Ueda, Weilin Gu, Hiromichi Dansako, Hironori Nishitsuji, Shinya Satoh, Kunitada Shimotohno, Nobuyuki Kato

    Biochemical and biophysical research communications   515 ( 1 )   156 - 162   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hepatitis B virus (HBV) infection, which increases the risk of cirrhosis and hepatocellular carcinoma and requires lifelong treatment, has become a major global health problem. However, host factors essential to the HBV life cycle are still unclear, and the development of new drugs is needed. Cells derived from the human hepatoma cell line HepG2 and engineered to overexpress sodium taurocholate cotransporting polypeptide (NTCP: a receptor for HBV), termed HepG2/NTCP cells, are widely used as the cell-based HBV infection and replication systems for HBV research. We recently found that human hepatoma cell line Li23-derived cells overexpressing NTCP (A8 cells subcloned from Li23 cells), whose gene expression profile was distinct from that of HepG2/NTCP cells, were also sensitive to HBV infection. However, the HBV susceptibility of A8 cells was around 1/100 that of HepG2/NTCP cells. Since we considered that plural cell assay systems will be needed for the objective evaluation of anti-HBV reagents, as we previously demonstrated in hepatitis C virus research, we here attempted to develop a new Li23 cell-derived assay system equivalent to that using HepG2/NTCP cells. By repeated subcloning of A8 cells, we successfully established a new cell line (A8.15.78.10) exhibiting high HBV susceptibility equal to that of HepG2/NTCP cells. Characterization of A8.15.78.10 cells revealed that the increase of HBV susceptibility was correlated with increases in the protein and glycosylation levels of NTCP, and with decreased expression of STING, a factor contributing to innate immunity. Finally, we performed a comparative evaluation of HBV entry inhibitors (cyclosporin A and rosiglitazone) by an HBV/secNL reporter assay using A8.15.78.10 cells or HepG2/NTCP cells. The results confirmed that cyclosporin A exhibited anti-HBV activity in both cell lines, as previously reported. However, we found that rosiglitazone did not show the anti-HBV activity in A8.15.78.10 cells, although it worked in HepG2/NTCP cells as previously reported. This suggested that the difference in anti-HBV activity between cyclosporin A and rosiglitazone was due to the different types of cells used for the assay. In conclusion, plural assay systems using different types of cells are required for the objective and impartial evaluation of anti-HBV reagents.

    DOI: 10.1016/j.bbrc.2019.05.126

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  • Ribavirin-induced down-regulation of CCAAT/enhancer-binding protein α leads to suppression of lipogenesis. 査読

    Satoh S, Onomura D, Ueda Y, Dansako H, Honda M, Kaneko S, Kato N

    The Biochemical journal   476 ( 1 )   137 - 149   2019年1月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1042/BCJ20180680

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  • High‐level expression of STING restricts susceptibility to HBV by mediating type III IFN induction. 査読

    Dansako H, Imai H, Ueda Y, Satoh S, Shimotohno K, Kato N

    FASEB BioAdvances   1 - 14   2018年11月

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    担当区分:筆頭著者, 責任著者  

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  • Multiple antiviral activities of the antimalarial and anti-hepatitis C drug candidates N-89 and N-251. 査読 国際誌

    Youki Ueda, Weilin Gu, Hiromichi Dansako, Hye-Sook Kim, Sayaka Yoshizaki, Nobuaki Okumura, Tomohiro Ishikawa, Hironori Nishitsuji, Fumihiro Kato, Takayuki Hishiki, Shinya Satoh, Koji Ishii, Michiaki Masuda, Kunitada Shimotohno, Masanori Ikeda, Nobuyuki Kato

    Biochemistry and biophysics reports   15   1 - 6   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The chemically synthesized endoperoxide compound N-89 and its derivative N-251 were shown to have potent antimalarial activity. We previously demonstrated that N-89 and N-251 potently inhibited the RNA replication of hepatitis C virus (HCV), which belongs to the Flaviviridae family. Since antimalarial and anti-HCV mechanisms have not been clarified, we were interested whether N-89 and N-251 possessed the activity against viruses other than HCV. In this study, we examined the effects of N-89 and N-251 on other flaviviruses (dengue virus and Japanese encephalitis virus) and hepatitis viruses (hepatitis B virus and hepatitis E virus). Our findings revealed that N-89 and N-251 moderately inhibited the RNA replication of Japanese encephalitis virus and hepatitis E virus, although we could not detect those anti-dengue virus activities. We also observed that N-89 and N-251 moderately inhibited the replication of hepatitis B virus at the step after viral translation. These results suggest the possibility that N-89 and N-251 act on some common host factor(s) that are necessary for viral replications, rather than the possibility that N-89 and N-251 directly act on the viral proteins except for HCV. We describe a new type of antiviral reagents, N-89 and N-251, which are applicable to multiple different viruses.

    DOI: 10.1016/j.bbrep.2018.05.007

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  • Daunorubicin, a topoisomerase II poison, suppresses viral production of hepatitis B virus by inducing cGAS-dependent innate immune response. 査読

    Imai H, Dansako H, Ueda Y, Satoh S, Kato N

    Biochemical and biophysical research communications   2018年9月

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    担当区分:責任著者  

    DOI: 10.1016/j.bbrc.2018.08.195

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  • ULBP1 is induced by hepatitis C virus infection and is the target of the NK cell-mediated innate immune response in human hepatocytes 査読

    Hiromichi Dansako, Hirotaka Imai, Youki Ueda, Shinya Satoh, Takaji Wakita, Nobuyuki Kato

    FEBS Open Bio   8 ( 3 )   361 - 371   2018年3月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley Blackwell  

    Natural killer (NK) cells through their NK group 2 member D (NKG2D) receptors recognize NKG2D ligands such as UL16-binding proteins (ULBPs) on virus-infected cells and subsequently trigger the host innate immune response. In the present study, we demonstrated that hepatitis C virus (HCV) induced the cell surface expression of ULBP1 in human immortalized hepatocyte PH5CH8 cells and human hepatoma HuH-7 cell-derived RSc cells. Interestingly, NK cell line NK-92 induced cytotoxicity and interferon-γ mRNA expression and subsequently reduced the levels of HCV RNA replication during co-culture with HCV-infected RSc cells. From these results, we conclude that ULBP1 is a target of the NK cell-mediated innate immune response in HCV-infected human hepatocytes.

    DOI: 10.1002/2211-5463.12373

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  • Ribavirin suppresses hepatic lipogenesis through inosine monophosphate dehydrogenase inhibition: Involvement of adenosine monophosphate-activated protein kinase-related kinases and retinoid X receptor α. 査読

    Satoh S, Mori K, Onomura D, Ueda Y, Dansako H, Honda M, Kaneko S, Ikeda M, Kato N

    Hepatology communications   1 ( 6 )   550 - 563   2017年8月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/hep4.1065

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  • Evaluation of preclinical antimalarial drugs, which can overcome direct acting antivirals-resistant hepatitis C viruses, using the viral reporter assay systems 査読

    Youki Ueda, Hiromichi Dansako, Shinya Satoh, Hye-Sook Kim, Yusuke Wataya, Hiroyuki Doi, Masanori Ikeda, Nobuyuki Kato

    VIRUS RESEARCH   235   37 - 48   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a major global health problem. Recently developed treatments with direct-acting antivirals (DAAs) have largely improved the sustained virologic response rate of patients with chronic hepatitis C. However, this approach is still hindered by its great expense and the problem of drug resistance. Using our cell-based HCV assay systems, we reported that the preclinical antimalarial drugs N-89 and N-251 exhibited potent anti-HCV activities. In this study we used our assay systems to evaluate the anti-HCV activities of six kinds of DAAs individually or in combination with N-89 or N-251. The results showed that the DAAs had potent anti-HCV activities and N-89 or N-251 contributed additive or synergistic effect. Using DAA-resistant HCV-RNA-replicating cells, which were prepared by continuous treatment with each DAA, we demonstrated that N-89 and N-251 could overcome all of the DAA-resistant HCVs. These preclinical drugs would have been potential as components of a therapeutic regimen that also included combinations of various DAAs. In addition, sequence analysis of the NS3-NS5B regions of the DAA-resistant HCV genomes newly found several amino acid (aa) substitutions that were suggested to contribute to DAA-resistance in addition to the aa substitutions already known to cause DAA-resistance. Among these new aa substitutions, we found that two substitutions in the NS3 region (D79G and S174Y) contributed to simeprevirand/or asunaprevir-resistance.

    DOI: 10.1016/j.virusres.2017.03.015

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  • Rab13 Is Involved in the Entry Step of Hepatitis C Virus Infection 査読

    Midori Takeda, Masanori Ikeda, Shinya Satoh, Hiromichi Dansako, Takaji Wakita, Nobuyuki Kato

    ACTA MEDICA OKAYAMA   70 ( 2 )   111 - 118   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Membrane transport probably participates in the lifecycle of hepatitis C virus (HCV). Rab proteins are essential host factors for HCV RNA replication, but these proteins' roles in other steps of the HCV lifecycle are not clear. The tight junction (TJ) plays a key role in HCV infection. Rab13 regulates the endocytic recycling of the TJ-associated proteins. Here we investigated whether Rab13 is involved in the HCV entry step. We used HuH-7-derived RSc cells and Li23-derived D7 cells. To evaluate the effect of Rab13 in HCV infection, we transfected the cells with siRNA targeting Rab13 before HCV infection. The down-regulation of Rab13 inhibited HCV infection. The D7 cells had showed a greater inhibitory effect against HCV infection compared to that in the RSc cells by Rab13 knockdown. Next, to evaluate the effect of Rab13 after infection, we inoculated the cells with HCV before transfection of the siRNA. The down-regulation of Rab13 did not show any effects after HCV infection. We further examined whether Rab13 would influence HCV RNA replication by using HCV replicon-harboring cells. The results revealed that Rab13 did not affect the step of HCV RNA replication. These results suggest that Rab13 plays an important role in the step of HCV entry.

    DOI: 10.18926/AMO/54190

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  • Molecular Mechanism Underlying the Suppression of CPB2 Expression Caused by Persistent Hepatitis C Virus RNA Replication 査読

    Hiroe Sejima, Shinya Satoh, Hiromichi Dansako, Masao Honda, Shuichi Kaneko, Masanori Ikeda, Nobuyuki Kato

    ACTA MEDICA OKAYAMA   70 ( 2 )   75 - 88   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    The mechanisms of hepatitis C virus (HCV)-associated hepatocarcinogenesis and disease progression are unclear. We previously observed that the expression level of carboxypeptidase B2 (CPB2) gene was remarkably suppressed by persistent HCV RNA replication in human hepatoma cell line Li23-derived cells. The results of the present study demonstrated that the CPB2 expression in patients with chronic hepatitis C was inversely correlated with several risk factors of hepatic fibrosis or steatosis, although ectopic CPB2 expression did not suppress the expression of fibrogenic or lipogenic genes. The suppressed CPB2 expression was restored by treatment with 5-azacytidine. To clarify the mechanism underlying this phenomenon, we analyzed the CPB2 promoter, and the results revealed that (1) hepatocyte nuclear factor 1 (HNF1), especially HNF1 alpha, was essential for the CPB2 promoter, and (2) CPB2 promoter was not methylated by persistent HCV RNA replication. The expression levels of HNF1 alpha and HNF1 beta were also not changed by persistent HCV RNA replication. These results suggest the existence of 5-azacytidine-inducible or -reducible unknown factor(s) that can control the CPB2 expression. To evaluate this idea we performed a microarray analysis, and several gene candidates corresponding to the suggested factor(s) were identified.

    DOI: 10.18926/AMO/54186

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  • The cyclic GMP-AMP synthetase-STING signaling pathway is required for both the innate immune response against HBV and the suppression of HBV assembly 査読

    Hiromichi Dansako, Youki Ueda, Nobuaki Okumura, Shinya Satoh, Masaya Sugiyama, Masashi Mizokami, Masanori Ikeda, Nobuyuki Kato

    FEBS JOURNAL   283 ( 1 )   144 - 156   2016年1月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    During viral replication, the innate immune response is induced through the recognition of viral replication intermediates by host factor(s). One of these host factors, cyclic GMP-AMP synthetase (cGAS), was recently reported to be involved in the recognition of viral DNA derived from DNA viruses. However, it is uncertain whether cGAS is involved in the recognition of hepatitis B virus (HBV), which is a hepatotropic DNA virus. In the present study, we demonstrated that HBV genome-derived double-stranded DNA induced the innate immune response through cGAS and its adaptor protein, stimulator of interferon genes (STING), in human hepatoma Li23 cells expressing high levels of cGAS. In addition, we demonstrated that HBV infection induced ISG56 through the cGAS-STING signaling pathway. This signaling pathway also showed an antiviral response towards HBV through the suppression of viral assembly. From these results, we conclude that the cGAS-STING signaling pathway is required for not only the innate immune response against HBV but also the suppression of HBV assembly. The cGAS-STING signaling pathway may thus be a novel target for anti-HBV strategies.

    DOI: 10.1111/febs.13563

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  • Annexin A1 Negatively Regulates Viral RNA Replication of Hepatitis C Virus 査読

    Hiroki Hiramoto, Hiromichi Dansako, Midori Takeda, Shinya Satoh, Takaji Wakita, Masanori Ikeda, Nobuyuki Kato

    ACTA MEDICA OKAYAMA   69 ( 2 )   71 - 78   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    Persistent infection with hepatitis C virus (HCV) often causes chronic hepatitis, and then shows a high rate of progression to liver cirrhosis and hepatocellular carcinoma. To clarify the mechanism of the persistent HCV infection is considered to be important for the discovery of new target(s) for the development of anti-HCV strategies. In the present study, we found that the expression level of annexin A1 (ANXA1) in human hepatoma cell line Li3-derived D7 cells was remarkably lower than that in parental Li23 cells, whereas the susceptibility of D7 cells to HCV infection was much higher than that of Li23 cells. Therefore, we hypothesized that ANXA1 negatively regulates persistent HCV infection through the inhibition of viral RNA replication. The results revealed that HCV production was significantly inhibited without a concomitant reduction in the amount of lipid droplets in the D7 cells stably expressing exogenous ANXAL Further, we demonstrated that ANXA1 negatively regulated the step of viral RNA replication rather than that of viral entry in human hepatocytes. These results suggest that ANXA1 would be a novel target for the development of anti-HCV strategies.

    DOI: 10.18926/AMO/53335

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  • Negative regulation of hepatitis B virus replication by forkhead box protein A in human hepatoma cells 査読

    Nobuaki Okumura, Masanori Ikeda, Shinya Satoh, Hiromichi Dansako, Masaya Sugiyama, Masashi Mizokami, Nobuyuki Kato

    FEBS LETTERS   589 ( 10 )   1112 - 1118   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Hepatitis B virus (HBV) replication is controlled by liver-enriched transcriptional factors, including forkhead box protein A (FOXA) members. Here, we found that FOXA members are directly and indirectly involved in HBV replication in human hepatic cells. HBV replication was elevated in HuH-7 treated with individual FOXA members-specific siRNA. Reciprocally, the downregulation of HBV replication was observed in FOXA-induced HuH-7. However, the mechanism of downregulation is different among FOXA members at the level of HBV RNA transcription, such as precore/pg RNA and 2.1 kb RNA. In addition, FOXA1 and FOXA2 suppressed nuclear hormone receptors, such as HNF4 alpha, that are related to HBV replication. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.febslet.2015.03.022

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  • [Recognition mechanism of hepatitis C viral infection]. 査読

    Dansako H, Kato N

    Nihon rinsho. Japanese journal of clinical medicine   73 ( 2 )   229 - 233   2015年2月

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  • Establishment of Hepatitis C Virus RNA-Replicating Cell Lines Possessing Ribavirin-Resistant Phenotype 査読

    Shinya Satoh, Kyoko Mori, Youki Ueda, Hiroe Sejima, Hiromichi Dansako, Masanori Ikeda, Nobuyuki Kato

    PLOS ONE   10 ( 2 )   e0118313   2015年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background
    Ribavirin (RBV) is a potential partner of interferon-based therapy and recently approved therapy using direct acting antivirals for patients with chronic hepatitis C. However, the precise mechanisms underlying RBV action against hepatitis C virus (HCV) replication are not yet understood. To clarify this point, we attempted to develop RBV-resistant cells from RBV-sensitive HCV RNA-replicating cells.
    Methodology/Principal Findings
    By repetitive RBV (100 mu M) treatment (10 weeks) of 3.5-year-cultured OL8 cells, in which genome-length HCV RNA (O strain of genotype 1b) efficiently replicates, dozens of colonies that survived RBV treatment were obtained. These colonies were mixed together and further treated with high doses of RBV (up to 200 mu M). By such RBV treatment, we successfully established 12 RBV-survived genome-length HCV RNA-replicating cell lines. Among them, three representative cell lines were characterized. HCV RNA replication in these cells resisted RBV significantly more than that in the parental OL8 cells. Genetic analysis of HCV found several common and conserved amino acid substitutions in HCV proteins among the three RBV-resistant cell species. Furthermore, using cDNA microarray and quantitative RT-PCR analyses, we identified 5 host genes whose expression levels were commonly altered by more than four-fold among these RBV-resistant cells compared with the parental cells. Moreover, to determine whether viral or host factor contributes to RBV resistance, we developed newly HCV RNA-replicating cells by introducing total RNAs isolated from RBV-sensitive parental cells or RBV-resistant cells into the HCV RNA-cured-parental or -RBV-resistant cells using an electroporation method, and evaluated the degrees of RBV resistance of these developed cells. Consequently, we found that RBV-resistant phenotype was conferred mainly by host factor and partially by viral factor.
    Conclusions/Significance
    These newly established HCV RNA-replicating cell lines should become useful tools for further understanding the anti-HCV mechanisms of RBV.

    DOI: 10.1371/journal.pone.0118313

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  • Rab18 is required for viral assembly of hepatitis C virus through trafficking of the core protein to lipid droplets 査読

    Hiromichi Dansako, Hiroki Hiramoto, Masanori Ikeda, Takaji Wakita, Nobuyuki Kato

    VIROLOGY   462   166 - 174   2014年8月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    During persistent infection of HCV, the HCV core protein (HCV-JFH-1 strain of genotype 2a) is recruited to lipid droplets (LDs) for viral assembly, but the mechanism of recruitment of the HCV core protein is uncertain. Here, we demonstrated that one of the Ras-related small GTPases, Rab18, was required for trafficking of the core protein around LDs. The knockdown of Rab18 reduced intracellular and extracellular viral infectivity, but not intracellular viral replication in HCV-JFH-1-infected RSc cells (an HuH-7-derived cell line). Exogenous expression of Rab18 increased extracellular viral infectivity almost two-fold. Furthermore, Rab18 was co-localized with the core protein in HCV-JFH-1-infected RSc cells, and the knockdown of Rab18 blocked recruitment of the HCV-JFH-1 core protein to LDs. These results suggest that Rab18 has an important role in viral assembly through the trafficking of the core protein to LDs. (C) 2014 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.virol.2014.05.017

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  • Anti-HCV activity of the Chinese medicinal fungus Cordyceps militaris 査読

    Youki Ueda, Kyoko Mori, Shinya Satoh, Hiromichi Dansako, Masanori Ikeda, Nobuyuki Kato

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   447 ( 2 )   341 - 345   2014年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although the sustained virologic response rate in the treatment of genotype 1 using new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has been improved by more than 70%, several severe side effects such as skin rash/ageusia and advanced anemia have become a problem. Under these circumstances, a new type of anti-HCV oral drug with few side effects is needed. Our recently developed HCV drug assay systems, including the HuH-7 cell line-derived OR6 and AH1R, and the Li23 cell line derived ORL8 and ORL11, allow genome-length HCV RNAs (several strains of genotype 1b) encoding renilla luciferase to replicate efficiently. Using these systems as anti-HCV candidates, we have identified numerous existing medicines that can be used against HCV with few side effects, such as statins and teprenon. To obtain additional anti-HCV candidates, we evaluated a number of oral health supplements, and found that the capsule but not the liquid form of Cordyceps militaris (CM) (Ascomycotinanorth, North Chinese caterpillar fungus), which is used as a Chinese herbal medicine, exhibited moderate anti-HCV activity. In combination with interferon-a or ribavirin, CM exhibited an additive inhibitory effect. Among the main components of CM, cordycepin, but not ergosterol, contributed to the anti-HCV activity of CM. In consideration of all these results, we suggest that CM would be useful as an oral anti-HCV agent in combination with interferon-alpha and/or ribavirin. (C) 2014 Elsevier Inc. All rights reserved.

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  • Genetic Characterization of Hepatitis C Virus in Long-Term RNA Replication Using Li23 Cell Culture Systems 査読

    Nobuyuki Kato, Hiroe Sejima, Youki Ueda, Kyoko Mori, Shinya Satoh, Hiromichi Dansako, Masanori Ikeda

    PLOS ONE   9 ( 3 )   e91156   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background: The most distinguishing genetic feature of hepatitis C virus (HCV) is its remarkable diversity and variation. To understand this feature, we previously performed genetic analysis of HCV in the long-term culture of human hepatoma HuH-7-derived HCV RNA-replicating cell lines. On the other hand, we newly established HCV RNA-replicating cell lines using human hepatoma Li23 cells, which were distinct from HuH-7 cells.
    Methodology/Principal Findings: Li23-derived HCV RNA-replicating cells were cultured for 4 years. We performed genetic analysis of HCVs recovered from these cells at 0, 2, and 4 years in culture. Most analysis was performed in two separate parts: one part covered from the 5'-terminus to NS2, which is mostly nonessential for RNA replication, and the other part covered from NS3 to NS5B, which is essential for RNA replication. Genetic mutations in both regions accumulated in a timedependent manner, and the mutation rates in the 5'-terminus-NS2 and NS3-NS5B regions were 4.0-9.0x10(-3) and 2.7-4.0x10(-3) base substitutions/site/year, respectively. These results suggest that the variation in the NS3-NS5B regions is affected by the pressure of RNA replication. Several in-frame deletions (3-105 nucleotides) were detected in the structural regions of HCV RNAs obtained from 2-year or 4-year cultured cells. Phylogenetic tree analyses clearly showed that the genetic diversity of HCV was expanded in a time-dependent manner. The GC content of HCV RNA was significantly increased in a time-dependent manner, as previously observed in HuH-7-derived cell systems. This phenomenon was partially due to the alterations in codon usages for codon optimization in human cells. Furthermore, we demonstrated that these long-term cultured cells were useful as a source for the selection of HCV clones showing resistance to anti-HCV agents.
    Conclusions/Significance: Long-term cultured HCV RNA-replicating cells are useful for the analysis of evolutionary dynamics and variations of HCV and for drug-resistance analysis.

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  • Co-immunoprecipitation of Flag-TLR3 or Myc-MSR1 with HCV RNA. 査読

    Yamane D, Dansako H, Lemon SM

    Bio-protocol   4 ( 4 )   2014年2月

  • New Preclinical Antimalarial Drugs Potently Inhibit Hepatitis C Virus Genotype 1b RNA Replication 査読

    Youki Ueda, Midori Takeda, Kyoko Mori, Hiromichi Dansako, Takaji Wakita, Hye-Sook Kim, Akira Sato, Yusuke Wataya, Masanori Ikeda, Nobuyuki Kato

    PLOS ONE   8 ( 8 )   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background: Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has recently been started and is expected to achieve a sustained virologic response of more than 70% in HCV genotype 1 patients, there are several problems to be resolved, including skin rash/ageusia and advanced anemia. Thus a new type of anti-HCV drug is still needed.
    Methodology/Principal Findings: Recently developed HCV drug assay systems using HCV-RNA-replicating cells (e.g., HuH-7-derived OR6 and Li23-derived ORL8) were used to evaluate the anti-HCV activity of drug candidates. During the course of the evaluation of anti-HCV candidates, we unexpectedly found that two preclinical antimalarial drugs (N-89 and its derivative N-251) showed potent anti-HCV activities at tens of nanomolar concentrations irrespective of the cell lines and HCV strains of genotype 1b. We confirmed that replication of authentic HCV-RNA was inhibited by these drugs. Interestingly, however, this anti-HCV activity did not work for JFH-1 strain of genotype 2a. We demonstrated that HCV-RNA-replicating cells were cured by treatment with only N-89. A comparative time course assay using N-89 and interferon-alpha demonstrated that N-89-treated ORL8 cells had more rapid anti-HCV kinetics than did interferon-alpha-treated cells. This anti-HCV activity was largely canceled by vitamin E. In combination with interferon-alpha and/or ribavirin, N-89 or N-251 exhibited a synergistic inhibitory effect.
    Conclusions/Significance: We found that the preclinical antimalarial drugs N-89 and N-251 exhibited very fast and potent anti-HCV activities using cell-based HCV-RNA-replication assay systems. N-89 and N-251 may be useful as a new type of anti-HCV reagents when used singly or in combination with interferon and/or ribavirin.

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  • New Preclinical Antimalarial Drugs Potently Inhibit Hepatitis C Virus Genotype 1b RNA Replication 査読

    Youki Ueda, Midori Takeda, Kyoko Mori, Hiromichi Dansako, Takaji Wakita, Hye-Sook Kim, Akira Sato, Yusuke Wataya, Masanori Ikeda, Nobuyuki Kato

    PLOS ONE   8 ( 8 )   e72519   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background: Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has recently been started and is expected to achieve a sustained virologic response of more than 70% in HCV genotype 1 patients, there are several problems to be resolved, including skin rash/ageusia and advanced anemia. Thus a new type of anti-HCV drug is still needed.
    Methodology/Principal Findings: Recently developed HCV drug assay systems using HCV-RNA-replicating cells (e.g., HuH-7-derived OR6 and Li23-derived ORL8) were used to evaluate the anti-HCV activity of drug candidates. During the course of the evaluation of anti-HCV candidates, we unexpectedly found that two preclinical antimalarial drugs (N-89 and its derivative N-251) showed potent anti-HCV activities at tens of nanomolar concentrations irrespective of the cell lines and HCV strains of genotype 1b. We confirmed that replication of authentic HCV-RNA was inhibited by these drugs. Interestingly, however, this anti-HCV activity did not work for JFH-1 strain of genotype 2a. We demonstrated that HCV-RNA-replicating cells were cured by treatment with only N-89. A comparative time course assay using N-89 and interferon-alpha demonstrated that N-89-treated ORL8 cells had more rapid anti-HCV kinetics than did interferon-alpha-treated cells. This anti-HCV activity was largely canceled by vitamin E. In combination with interferon-alpha and/or ribavirin, N-89 or N-251 exhibited a synergistic inhibitory effect.
    Conclusions/Significance: We found that the preclinical antimalarial drugs N-89 and N-251 exhibited very fast and potent anti-HCV activities using cell-based HCV-RNA-replication assay systems. N-89 and N-251 may be useful as a new type of anti-HCV reagents when used singly or in combination with interferon and/or ribavirin.

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  • Class A Scavenger Receptor 1 (MSR1) Restricts Hepatitis C Virus Replication by Mediating Toll-like Receptor 3 Recognition of Viral RNAs Produced in Neighboring Cells 査読

    Hiromichi Dansako, Daisuke Yamane, Christoph Welsch, David R. McGivern, Fengyu Hu, Nobuyuki Kato, Stanley M. Lemon

    PLoS Pathogens   9 ( 5 )   e1003345   2013年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Persistent infections with hepatitis C virus (HCV) may result in life-threatening liver disease, including cirrhosis and cancer, and impose an important burden on human health. Understanding how the virus is capable of achieving persistence in the majority of those infected is thus an important goal. Although HCV has evolved multiple mechanisms to disrupt and block cellular signaling pathways involved in the induction of interferon (IFN) responses, IFN-stimulated gene (ISG) expression is typically prominent in the HCV-infected liver. Here, we show that Toll-like receptor 3 (TLR3) expressed within uninfected hepatocytes is capable of sensing infection in adjacent cells, initiating a local antiviral response that partially restricts HCV replication. We demonstrate that this is dependent upon the expression of class A scavenger receptor type 1 (MSR1). MSR1 binds extracellular dsRNA, mediating its endocytosis and transport toward the endosome where it is engaged by TLR3, thereby triggering IFN responses in both infected and uninfected cells. RNAi-mediated knockdown of MSR1 expression blocks TLR3 sensing of HCV in infected hepatocyte cultures, leading to increased cellular permissiveness to virus infection. Exogenous expression of Myc-MSR1 restores TLR3 signaling in MSR1-depleted cells with subsequent induction of an antiviral state. A series of conserved basic residues within the carboxy-terminus of the collagen superfamily domain of MSR1 are required for binding and transport of dsRNA, and likely facilitate acidification-dependent release of dsRNA at the site of TLR3 expression in the endosome. Our findings reveal MSR1 to be a critical component of a TLR3-mediated pattern recognition receptor response that exerts an antiviral state in both infected and uninfected hepatocytes, thereby limiting the impact of HCV proteins that disrupt IFN signaling in infected cells and restricting the spread of HCV within the liver. © 2013 Dansako et al.

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  • 骨粗鬆症治療剤であるラロキシフェンの抗HCV活性機構について 査読

    武田 緑, 池田 正徳, 森 京子, 矢野 雅彦, 有海 康雄, 團迫 浩方, 脇田 隆字, 加藤 宣之

    肝臓   54 ( Suppl.1 )   A340 - A340   2013年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • PML tumor suppressor protein is required for HCV production 査読

    Misao Kuroki, Yasuo Ariumi, Makoto Hijikata, Masanori Ikeda, Hiromichi Dansako, Takaji Wakita, Kunitada Shimotohno, Nobuyuki Kato

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   430 ( 2 )   592 - 597   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    PML tumor suppressor protein, which forms discrete nuclear structures termed PML-nuclear bodies, has been associated with several cellular functions, including cell proliferation, apoptosis and antiviral defense. Recently, it was reported that the HCV core protein colocalizes with PML in PML-NBs and abrogates the PML function through interaction with PML. However, role(s) of PML in HCV life cycle is unknown. To test whether or not PML affects HCV life cycle, we examined the level of secreted HCV core and the infectivity of HCV in the culture supernatants as well as the level of HCV RNA in HuH-7-derived RSc cells, in which HCV-JFH1 can infect and efficiently replicate, stably expressing short hairpin RNA targeted to PML. In this context, the level of secreted HCV core and the infectivity in the supernatants from PML knockdown cells was remarkably reduced, whereas the level of HCV RNA in the PML knockdown cells was not significantly affected in spite of very effective knockdown of PML. In fact, we showed that PML is unrelated to HCV RNA replication using the subgenomic HCV-JFH1 replicon RNA, JRN/3-5B. Furthermore, the infectivity of HCV-like particle in the culture supernatants was significantly reduced in PML knockdown JRN/3-5B cells expressing core to NS2 coding region of HCV-JFH1 genome using the trans-packaging system. Finally, we also demonstrated that INI1 and DDX5, the PML-related proteins, are involved in HCV production. Taken together, these findings suggest that PML is required for HCV production. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2012.11.108

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  • Development of a drug assay system with hepatitis C virus genome derived from a patient with acute hepatitis C 査読

    Kyoko Mori, Youki Ueda, Yasuo Ariumi, Hiromichi Dansako, Masanori Ikeda, Nobuyuki Kato

    VIRUS GENES   44 ( 3 )   374 - 381   2012年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    We developed a new cell culture drug assay system (AH1R), in which genome-length hepatitis C virus (HCV) RNA (AH1 strain of genotype 1b derived from a patient with acute hepatitis C) efficiently replicates. By comparing the AH1R system with the OR6 assay system that we developed previously (O strain of genotype 1b derived from an HCV-positive blood donor), we demonstrated that the anti-HCV profiles of reagents including interferon-gamma and cyclosporine A significantly differed between these assay systems. Furthermore, we found unexpectedly that rolipram, an anti-inflammatory drug, showed anti-HCV activity in the AH1R assay but not in the OR6 assay, suggesting that the anti-HCV activity of rolipram differs depending on the HCV strain. Taken together, these results suggest that the AH1R assay system is useful for the objective evaluation of anti-HCV reagents and for the discovery of different classes of anti-HCV reagents.

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  • Raloxifene inhibits hepatitis C virus infection and replication 査読

    Midori Takeda, Masanori Ikeda, Kyoko Mori, Masahiko Yano, Yasuo Ariumi, Hiromichi Dansako, Takaji Wakita, Nobuyuki Kato

    FEBS OPEN BIO   2   279 - 283   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE LONDON  

    Postmenopausal women with chronic hepatitis C exhibited a poor response to interferon (IFN) therapy compared to premenopausal women. Osteoporosis is the typical complication that occurs in postmenopausal women. Recently, it was reported that an osteoporotic reagent, vitamin D3, exhibited anti-hepatitis C virus (HCV) activity. Therefore, we investigated whether or not another osteoporotic reagent, raloxifene, would exhibit anti-HCV activity in cell culture systems. Here, we demonstrated that raloxifene inhibited HCV RNA replication in genotype 1b and infection in genotype 2a. Raloxifene enhanced the anti-HCV activity of IFN-alpha . These results suggest a link between the molecular biology of osteoporosis and the HCV life cycle. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

    DOI: 10.1016/j.fob.2012.08.003

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  • Anti-ulcer agent teprenone inhibits hepatitis C virus replication: potential treatment for hepatitis C 査読

    Masanori Ikeda, Yoshinari Kawai, Kyoko Mori, Masahiko Yano, Ken-ichi Abe, Go Nishimura, Hiromichi Dansako, Yasuo Ariumi, Takaji Wakita, Kazuhide Yamamoto, Nobuyuki Kato

    LIVER INTERNATIONAL   31 ( 6 )   873 - 882   2011年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Background
    Previously we reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, inhibited hepatitis C virus (HCV) RNA replication. Furthermore, recent reports revealed that the statins are associated with a reduced risk of hepatocellular carcinoma and lower portal pressure in patients with cirrhosis. The statins exhibited anti-HCV activity by inhibiting geranylgeranylation of host proteins essential for HCV RNA replication. Geranylgeranyl pyrophosphate (GGPP) is a substrate for geranylgeranyltransferase. Therefore, we examined the potential of geranyl compounds with chemical structures similar to those of GGPP to inhibit HCV RNA replication.
    Methods
    We tested geranyl compounds [geranylgeraniol, geranylgeranoic acid, vitamin K(2) and teprenone (Selbex)] for their effects on HCV RNA replication using genome-length HCV RNA-replicating cells (the OR6 assay system) and a JFH-1 infection cell culture system. Teprenone is the major component of the anti-ulcer agent, Selbex. We also examined the anti-HCV activities of the geranyl compounds in combination with interferon (IFN)-alpha or statins.
    Results
    Among the geranyl compounds tested, only teprenone exhibited anti-HCV activity at a clinically achievable concentration. However, other anti-ulcer agents tested had no inhibitory effect on HCV RNA replication. The combination of teprenone and IFN-alpha exhibited a strong inhibitory effect on HCV RNA replication. Although teprenone alone did not inhibit geranylgeranylation, surprisingly, statins' inhibitory action against geranylgeranylation was enhanced by cotreatment with teprenone.
    Conclusions
    The anti-ulcer agent teprenone inhibited HCV RNA replication and enhanced statins' inhibitory action against geranylgeranylation. This newly discovered function of teprenone may improve the treatment of HCV-associated liver diseases as an adjuvant to statins.

    DOI: 10.1111/j.1478-3231.2011.02499.x

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  • Mechanism of action of ribavirin in a novel hepatitis C virus replication cell system 査読

    Kyoko Mori, Masanori Ikeda, Yasuo Ariumi, Hiromichi Dansako, Takaji Wakita, Nobuyuki Kato

    VIRUS RESEARCH   157 ( 1 )   61 - 70   2011年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Ribavirin (RBV) is a potential partner of interferon (IFN)-based therapy for patients with chronic hepatitis C. However, to date, its anti-hepatitis C virus (HCV) mechanism remains ambiguous due to the marginal activity of RBV on HCV RNA replication in HuH-7-derived cells, which are currently used as the only cell culture system for robust HCV replication. We investigated the anti-HCV activity of RBV using novel cell assay systems. The recently discovered human hepatoma cell line, Li23, which enables robust HCV replication, and the recently developed Li23-derived drug assay systems (ORL8 and ORL11), in which the genome-length HCV RNA (O strain of genotype 1b) encoding renilla luciferase efficiently replicates, were used for this study. At clinically achievable concentrations, RBV unexpectedly inhibited HCV RNA replication in ORL8 and ORL11 systems, but not in OR6 (an HuH-7-derived assay system). The anti-HCV activity of RBV was almost cancelled by an inhibitor of equilibrative nucleoside transporters. The evaluation of the anti-HCV mechanisms of RBV proposed to date using ORL8 ruled out the possibility that RBV induces error catastrophe, the IFN-signaling pathway or oxidative stress. However, we found that the anti-HCV activity of RBV was efficiently cancelled with guanosine, and demonstrated that HCV RNA replication was notably suppressed in inosine monophosphate dehydrogenase (IMPDH)-knockdown cells, suggesting that the antiviral activity of RBV is mediated through the inhibition of IMPDH. In conclusion, we demonstrated for the first time that inhibition of IMPDH is a major antiviral target by which RBV at clinically achievable concentrations inhibits HCV RNA replication. (C) 2011 Elsevier B.V. All rights reserved.

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  • The ESCRT System Is Required for Hepatitis C Virus Production 査読

    Yasuo Ariumi, Misao Kuroki, Masatoshi Maki, Masanori Ikeda, Hiromichi Dansako, Takaji Wakita, Nobuyuki Kato

    PLOS ONE   6 ( 1 )   e14517   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background: Recently, lipid droplets have been found to be involved in an important cytoplasmic organelle for hepatitis C virus (HCV) production. However, the mechanisms of HCV assembly, budding, and release remain poorly understood. Retroviruses and some other enveloped viruses require an endosomal sorting complex required for transport (ESCRT) components and their associated proteins for their budding process.
    Methodology/Principal Findings: To determine whether or not the ESCRT system is needed for HCV production, we examined the infectivity of HCV or the Core levels in culture supernatants as well as HCV RNA levels in HuH-7-derived RSc cells, in which HCV-JFH1 can infect and efficiently replicate, expressing short hairpin RNA or siRNA targeted to tumor susceptibility gene 101 (TSG101), apoptosis-linked gene 2 interacting protein X (Alix), Vps4B, charged multivesicular body protein 4b (CHMP4b), or Brox, all of which are components of the ESCRT system. We found that the infectivity of HCV in the supernatants was significantly suppressed in these knockdown cells. Consequently, the release of the HCV Core into the culture supernatants was significantly suppressed in these knockdown cells after HCV-JFH1 infection, while the intracellular infectivity and the RNA replication of HCV-JFH1 were not significantly affected. Furthermore, the HCV Core mostly colocalized with CHMP4b, a component of ESCRT-III. In this context, HCV Core could bind to CHMP4b. Nevertheless, we failed to find the conserved viral late domain motif, which is required for interaction with the ESCRT component, in the HCV-JFH1 Core, suggesting that HCV Core has a novel motif required for HCV production.
    Conclusions/Significance: These results suggest that the ESCRT system is required for infectious HCV production.

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  • Amino acid substitutions of hepatitis C virus core protein are not associated with intracellular antiviral response to interferon-α in vitro. 査読

    Ikeda F, Dansako H, Nishimura G, Mori K, Kawai Y, Ariumi Y, Miyake Y, Takaki A, Nouso K, Iwasaki Y, Ikeda M, Kato N, Yamamoto K

    Liver international : official journal of the International Association for the Study of the Liver   30 ( 9 )   1324 - 1331   2010年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • C型肝炎ウイルスに対する新しい抗ウイルス剤スクリーニング系の開発 査読

    池田 正徳, 森 京子, 中澤 貴秀, 有海 康雄, 団迫 浩方, 加藤 宣之

    肝臓   51 ( Suppl.2 )   A586 - A586   2010年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • ヒト肝癌細胞株Li23由来の新しいHCV-RNA複製システムを用いたリバビリンの作用機序の解明 査読

    森 京子, 池田 正徳, 有海 康雄, 團迫 浩方, 加藤 宣之

    肝臓   51 ( Suppl.2 )   A586 - A586   2010年9月

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  • 新しいHCV-RNA複製系を用いたリバビリンの抗HCVメカニズムの解明(Mechanism of anti-HCV of ribavirin in a novel HCV replication cell system) 査読

    森 京子, 池田 正徳, 有海 康雄, 団迫 浩方, 加藤 宣之

    日本癌学会総会記事   69回   91 - 91   2010年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • がん抑制因子PMLはHCV生活環に必須である(The PML tumor suppressor protein is required for HCV life cycle) 査読

    黒木 美沙緒, 有海 康雄, 池田 正徳, 團迫 浩方, 脇田 隆字, 加藤 宣之

    日本癌学会総会記事   69回   91 - 91   2010年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • DNA損傷センサーATMキナーゼとChk2はC型肝炎ウイルスのRNA複製に必要である 査読

    有海 康雄, 黒木 美沙緒, 團迫 浩方, 阿部 健一, 池田 正徳, 脇田 隆字, 加藤 宣之

    岡山医学会雑誌   122 ( 1 )   9 - 16   2010年4月

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    記述言語:日本語   出版者・発行元:岡山医学会  

    HCV感染の機序として、DNAゲノムを保持するウイルスが感染細胞内のDNA損傷応答経路を活性化し、ウイルスの自己複製に利用していることが知られている。また、RNAゲノムしか保持しないHCVであっても、その感染により宿主細胞に二重鎖DNA切断を誘導し、宿主ゲノムを変異させていることが報告されている。今回、RNAゲノムしか保持していないHCVの複製にもDNA損傷応答経路が関与しているか否かを検討した結果、関与していることが示唆された。すなわち、DNA損傷センサーであるATMとChk2はHCV RNA複製に必要な宿主因子であることが明らかになった。

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  • Efficient replication systems for hepatitis C virus using a new human hepatoma cell line 査読

    Nobuyuki Kato, Kyoko Mori, Ken-ichi Abe, Hiromichi Dansako, Misao Kuroki, Yasuo Ariumi, Takaji Wakita, Masanori Ikeda

    VIRUS RESEARCH   146 ( 1-2 )   41 - 50   2009年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a serious global health problem. Cell culture-based persistent HCV RNA replication systems and infectious HCV production systems are widely used in HCV research. However, persistent HCV production systems have been developed only for HuH-7 hepatoma cells. Here we found a new human hepatoma cell line, Li23, that enables persistent HCV production and anti-HCV reagent assay. Li23's cDNA expression profile differed from HuH-7's, although the two cells had similar liver-specific expression profiles. We used HCV RNA with a specific combination of adaptive mutations to develop an HCV replicon system and genome-length HCV RNA replicating systems including a reporter assay system. Finally, Li23-derived cells persistently produced infectious virus of an HCV strain. Li23-derived cells are potentially useful for understanding the HCV life cycle and for finding antiviral targets. (C) 2009 Elsevier B.V. All rights reserved.

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  • HCV genotype 1b chimeric replicon with NS5B of JFH-1 exhibited resistance to cyclosporine A 査読

    Ken-ichi Abe, Masanori Ikeda, Yasuo Ariumi, Hiromichi Dansako, Takaji Wakita, Nobuyuki Kato

    ARCHIVES OF VIROLOGY   154 ( 10 )   1671 - 1677   2009年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER WIEN  

    Cyclosporine A (CsA) is a well-characterized anti-HCV reagent. Recently it was reported that the genotype 2a JFH-1 strain was more resistant than genotype 1 HCV strains to CsA in a cell culture system. However, the JFH-1 responsible region for the resistance to CsA remains unclear. It was also demonstrated that in genotype 1b HCVs, NS5B interacts with cyclophilin (CyP). To clarify whether or not NS5B of JFH-1 is significant for CsA resistance, we developed a chimeric replicon with NS5B of JFH-1 in the genotype 1b backbone. The chimeric replicon was more resistant to CsA than the parental genotype 1b replicon. Furthermore, reduction of CyPA had a greater effect on HCV RNA replication and sensitivity to CsA than reduction of CyPB. Here, we demonstrated that NS5B of JFH-1 contributed to this strain's CsA-resistant phenotype. NS5B and CyPA are significant for determining HCV's sensitivity to CsA.

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  • HCVコア蛋白質のアミノ酸の違いとIFN応答性との関係についての培養細胞を用いた解析 査読

    池田 房雄, 団迫 浩方, 西村 剛, 河合 良成, 有海 康雄, 池田 正徳, 高木 章乃夫, 岩崎 良章, 加藤 宣之, 山本 和秀

    肝臓   50 ( Suppl.2 )   A515 - A515   2009年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Development of a hepatitis C virus relapse model using genome-length hepatitis C virus ribonucleic acid-harboring cells possessing the interferon-alpha-resistance phenotype 査読

    Yoshinari Kawai, Masanori Ikeda, Ken-ichi Abe, Masahiko Yano, Yasuo Ariumi, Hiromichi Dansako, Kazuhide Yamamoto, Nobuyuki Kato

    HEPATOLOGY RESEARCH   39 ( 9 )   898 - 909   2009年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Aim:
    The cure rate of current interferon (IFN) therapy is limited to approximately 50% and most of the relapses after therapy are caused by genotype-1. To develop a relapse model in cell culture, we attempted to obtain genome-length hepatitis C virus ribonucleic acid (HCV RNA) harboring cells possessing the IFN-alpha-resistance phenotype from previously established OR6 cells, which enabled the luciferase reporter assay for monitoring of HCV RNA replication.
    Methods:
    The IFN-alpha-resistant HCV RNA-harboring cells and control cells were obtained by the treatment of OR6 cells with and without IFN-alpha, respectively. Then, we examined the relapse of HCV in IFN-alpha-resistant HCV RNA-harboring cells.
    Results:
    Only type I IFN (alpha and beta) showed significantly different anti-HCV activity between IFN-alpha-resistant HCV RNA-harboring cells and control cells. There was no significant difference in the anti-HCV activity of IFN-gamma, fluvastatin, or cyclosporine A between the two types of cells. Furthermore, we showed that fluvastatin or cyclosporine A in combination with IFN-alpha could prevent the relapse after therapy in the IFN-alpha-resistant HCV RNA-harboring cells.
    Conclusion:
    We developed a HCV relapse model in cell culture using IFN-alpha-resistant HCV RNA-harboring cells. Thus anti-HCV reagents, which have a mechanism different from IFN-alpha, were shown to be useful for preventing a relapse of IFN-alpha-resistant HCV.

    DOI: 10.1111/j.1872-034X.2009.00525.x

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  • Oxidative Stress Induces Anti-Hepatitis C Virus Status via the Activation of Extracellular Signal-Regulated Kinase 査読

    Masahiko Yano, Masanori Ikeda, Ken-ichi Abe, Yoshinari Kawai, Misao Kuroki, Kyoko Mori, Hiromichi Dansako, Yasuo Ariumi, Shougo Ohkoshi, Yutaka Aoyagi, Nobuyuki Kato

    HEPATOLOGY   50 ( 3 )   678 - 688   2009年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOHN WILEY & SONS INC  

    Recently, we reported that beta-carotene, vitamin D(2), and linoleic acid inhibited hepatitis C virus (HCV) RNA replication in hepatoma. cells. Interestingly, in the course of the study, we found that the antioxidant vitamin E negated the anti-HCV activities of these nutrients. These results suggest that the oxidative stress caused by the three nutrients is involved m their anti-HCV activities. However, the molecular mechanism by which oxidative stress induces anti-HCV status remains unknown. Oxidative stress is also known to activate extracellular signal-regulated kinase (ERK). Therefore, we hypothesized that oxidative stress induces anti-HCV status via the mitogen activated protein kinase (MAPK)/ERK kinase (MEK)-ERK1/2 signaling pathway. In this study, we found that the MEK1/2-spedfic inhibitor U0126 abolished the anti-HCV activities of the three nutrients in a dose-dependent manner. Moreover, U0126 significantly attenuated the anti-HCV activities of polyunsaturated fatty acids, interferon-gamma, and cyclosporine A, but not statins. We further demonstrated that, with the exception of the statins, all of these anti-HCV nutrients and reagents actually induced activation of the MEK-ERK1/2 signaling pathway, which was inhibited or reduced by treatment not only with U0126 but also with vitamin E We also demonstrated that phosphorylation of ERK1/2 by cyclosporine A was attenuated with N-acetylcysteine treatment and led to the negation of inhibition of HCV RNA replication. We propose that a cellular process that follows ERK1/2 phosphorylation and is specific to oxidative stimulation might lead to down-regulation of HCV RNA replication. Conclusion: Our results demonstrate the involvement of the MEK-ERK1/2 signaling pathway in the anti-HCV status induced by oxidative stress in a broad range of anti-HCV reagents. This intracellular modulation is expected to be a therapeutic target for the suppression of HCV RNA replication. (HEPATOLOGY 2009;50: 678-688.)

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  • Double-stranded RNA-induced interferon-beta and inflammatory cytokine production modulated by hepatitis C virus serine proteases derived from patients with hepatic diseases 査読

    Hiromichi Dansako, Masanori Ikeda, Yasuo Ariumi, Takaji Wakita, Nobuyuki Kato

    ARCHIVES OF VIROLOGY   154 ( 5 )   801 - 810   2009年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER WIEN  

    We previously demonstrated that hepatitis C virus (HCV) serine protease NS3-4A was unable to cleave TRIF (adaptor protein of Toll-like receptor 3), resulting in a lack of suppression of the TRIF-mediated pathway, whereas NS3-4A cleaved Cardif (adaptor protein of retinoic acid-inducible gene I or melanoma differentiation-associated gene-5), resulting in an interruption of the Cardif-mediated pathway in non-neoplastic human hepatocyte PH5CH8 cells. To elucidate these observations, we examined the cleavage potential of NS3-4A for TRIF in PH5CH8 cells, genome-length HCV RNA-replicating O cells, and HCV-infected cells, and we demonstrated that NS3-4A lacked the ability to cleave endogenous TRIF, regardless of HCV strains derived from patients with different stages of hepatic disease. Furthermore, we demonstrated that inflammatory cytokine production by NF-kappa B activation via the TRIF-mediated pathway also remained unsuppressed by NS3-4A. These results suggest that the inhibitory effects of NS3-4A on antiviral signaling pathways are limited to the Cardif-mediated pathway in human hepatocytes.

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  • Oncostatin M synergistically inhibits HCV RNA replication in combination with interferon-alpha 査読

    Masanori Ikeda, Kyoko Mori, Yasuo Ariumi, Hiromichi Dansako, Nobuyuki Kato

    FEBS LETTERS   583 ( 9 )   1434 - 1438   2009年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Oncostatin M (OSM), a member of the interleukin-6 family, possesses various functions, including hepatocyte differentiation and suppression of melanoma cell growth. Here, we report anti-hepatitis C virus (HCV) activity of OSM as a new function of this cytokine. OSM possessed marked anti-HCV activity (50% effective concentration: 0.71 ng/ml) in an HCV RNA replication cell culture system. The most striking finding is that OSM exhibited synergistic inhibitory activity on interferon (IFN)-alpha even at a low concentration with weak anti-HCV activity, such as 25 pg/ml. OSM is a candidate anti-HCV reagent and may improve the current IFN therapy for patients with chronic hepatitis C. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

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  • Replicons from genotype 1b HCV-positive sera exhibit diverse sensitivities to anti-HCV reagents 査読

    Go Nishimura, Masanori Ikeda, Kyoko Mori, Takahide Nakazawa, Yasuo Ariumi, Hiromichi Darisako, Nobuyuki Kato

    ANTIVIRAL RESEARCH   82 ( 1 )   42 - 50   2009年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Half of the population of genotype 1 HCV is resistant to current pegylated-interferon-alpha (PEG-IFN-alpha) and ribavirin therapy. The resistance to IFN therapy is an urgent problem, especially in patients with genotype I HCV infection. However, sensitivities among HCV strains to anti-HCV reagents including IFNs have not been thoroughly addressed. Here, we established three different subgenomic replicons (1B-4, 1B-5, and KAH5 strains) in addition to our previously established replicon (0 strain). We comparatively examined the sensitivities of four replicons to IFN-alpha, IFN-gamma, IFN-lambda, cyclosporine A, and fluvastatin. Among the replicons, the 1B-4 and KAH5 replicons were the most sensitive and resistant, respectively to IFN-lambda (EC(50): 1.50 ng/ml vs. 8.50 ng/ml) and fluvastatin (EC(50): 2.82 mu M vs. 7.87 mu M), although these replicons possessed similar features in terms of genetic distance from the 0 strain, HCV RNA expression levels, and sensitivity to IFN-alpha (EC(50): 1.44 IU/ml vs. 1.37 IU/ml) and cyclosporine A (EC(50): 0.71 mu g/ml vs. 0.96 mu g/ml). These replicons are thus useful tools for examining the mechanism of anti-HCV activity, especially in IFN-lambda and statins. (C) 2009 Elsevier B.V. All rights reserved.

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  • Arsenic Trioxide Inhibits Hepatitis C Virus RNA Replication through Modulation of the Glutathione Redox System and Oxidative Stress 査読

    Misao Kuroki, Yasuo Ariumi, Masanori Ikeda, Hiromichi Dansako, Takaji Wakita, Nobuyuki Kato

    JOURNAL OF VIROLOGY   83 ( 5 )   2338 - 2348   2009年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    Arsenic trioxide (ATO), a therapeutic reagent used for the treatment of acute promyelocytic leukemia, has recently been reported to increase human immunodeficiency virus type 1 infectivity. However, in this study, we have demonstrated that replication of genome-length hepatitis C virus (HCV) RNA (O strain of genotype 1b) was notably inhibited by ATO at submicromolar concentrations without cell toxicity. RNA replication of HCV-JFH1 (genotype 2a) and the release of core protein into the culture supernatants were also inhibited by ATO after the HCV infection. To clarify the mechanism of the anti-HCV activity of ATO, we examined whether or not PML is associated with this anti-HCV activity, since PML is known to be a target of ATO. Interestingly, we observed the cytoplasmic translocation of PML after treatment with ATO. However, ATO still inhibited the HCV RNA replication even in the PML knockdown cells, suggesting that PML is dispensable for the anti-HCV activity of ATO. In contrast, we found that N-acetyl-cysteine, an antioxidant and glutathione precursor, completely and partially eliminated the anti-HCV activity of ATO after 24 h and 72 h of treatment, respectively. In this context, it is worth noting that we found an elevation of intracellular superoxide anion radical, but not hydrogen peroxide, and the depletion of intracellular glutathione in the ATO-treated cells. Taken together, these findings suggest that ATO inhibits the HCV RNA replication through modulation of the glutathione redox system and oxidative stress.

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  • Genetic variability and diversity of intracellular genome-length hepatitis C virus RNA in long-term cell culture 査読

    Nobuyuki Kato, K. Abe, K. Mori, Y. Ariumi, H. Dansako, M. Ikeda

    ARCHIVES OF VIROLOGY   154 ( 1 )   77 - 85   2009年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER WIEN  

    Hepatitis C virus (HCV) is known to circulate persistently in vivo as a complex population of different but closely related viral variants. To understand the quasispecies nature of HCV, we performed genetic analysis of intracellular HCV RNAs obtained in long-term cell culture of genome-length HCV-RNA-replicating cells. The results revealed that genetic mutations in HCV RNAs accumulated in a time-dependent manner, and that the mutation rates of HCV RNAs were 3.5-4.8 x 10(-3) base substitutions/site/year. The mutation rates of nonstructural regions that are essential for RNA replication were lower than those of structural regions. The genetic diversity of HCVs was also enlarged in a time-dependent manner. Furthermore, we found that the GC content of HCV RNA was increased in a time-dependent manner. These results suggest that an HCV-RNA-replicating cell culture system would be useful for analysis of the evolutionary dynamics and variations of HCV.

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  • The DNA damage sensors ataxia-telangiectasia mutated kinase and checkpoint kinase 2 are required for hepatitis C virus RNA replication 査読

    Yasuo Ariumi, Misao Kuroki, Hiromichi Dansako, Ken-Ichi Abe, Masanori Ikeda, Takaji Wakita, Nobuyuki Kato

    JOURNAL OF VIROLOGY   82 ( 19 )   9639 - 9646   2008年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    Cellular responses to DNA damage are crucial for maintaining genome integrity, virus infection, and preventing the development of cancer. Hepatitis C virus (HCV) infection and the expression of the HCV nonstructural protein NS3 and core protein have been proposed as factors involved in the induction of double-stranded DNA breaks and enhancement of the mutation frequency of cellular genes. Since DNA damage sensors, such as the ataxia-telangiectasia mutated kinase (ATM), ATM-and Rad3-related kinase (ATR), poly(ADP-ribose) polymerase 1 (PARP-1), and checkpoint kinase 2 (Chk2), play central roles in the response to genotoxic stress, we hypothesized that these sensors might affect HCV replication. To test this hypothesis, we examined the level of HCV RNA in HuH-7-derived cells stably expressing short hairpin RNA targeted to ATM, ATR, PARP-1, or Chk2. Consequently, we found that replication of both genome-length HCV RNA (HCV-O, genotype 1b) and the subgenomic replicon RNA were notably suppressed in ATM-or Chk2-knockdown cells. In addition, the RNA replication of HCV-JFH1 (genotype 2a) and the release of core protein into the culture supernatants were suppressed in these knockdown cells after inoculation of the cell culture-generated HCV. Consistent with these observations, ATM kinase inhibitor could suppress the HCV RNA replication. Furthermore, we observed that HCV NS3-NS4A interacted with ATM and that HCV NS5B interacted with both ATM and Chk2. Taken together, these results suggest that the ATM signaling pathway is critical for HCV RNA replication and may represent a novel target for the clinical treatment of patients with chronic hepatitis C.

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  • A new living cell-based assay system for monitoring genome-length hepatitis C virus RNA replication 査読

    Hiromichi Dansako, Masanori Ikeda, Ken-ichi Abe, Kyoko Mori, Kazunori Takemoto, Yasuo Ariumi, Nobuyuki Kato

    VIRUS RESEARCH   137 ( 1 )   72 - 79   2008年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    We previously developed a cell-based luciferase reporter assay system for monitoring genome-length hepatitis C virus (HCV) RNA replication (OR6 assay system). Here. we aimed to develop a new living cell-based reporter assay system using enhanced green fluorescent protein (EGFP). Genome-length HCV RNAs encoding EGFP were introduced into a subline of HuH-7 cells and G418 selection was performed. One cloned cell line, OGF7, was successfully selected from among the several G418-resistant cell lines obtained, and the robust expression of HCV RNA and proteins in OGF7 cells was confirmed. The fluorescent intensity of OGF7 cells was decreased by interferon-alpha treatment in a dose-dependent manner, and it correlated well with the HCV RNA concentration. We demonstrated that the interferon-alpha sensitivity in the OGF7 assay system measuring the fluorescent intensity was equivalent to that of the OR6 assay system, and that the OGF7 assay system Was useful for quantitative evaluation of anti-HCV reagents. The OGF7 assay system is expected to be the most time-saving and inexpensive assay system for high-throughput screening of anti-HCV reagents. (C) 2008 Elsevier B.V. All rights reserved.

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  • 急性C型肝炎患者由来の新しいC型肝炎ウイルスゲノム複製系(New efficient replication system with hepatitis C virus genome derived from a patient with acute hepatitis C) 査読

    森 京子, 阿部 健一, 團迫 浩方, 有海 康雄, 池田 正徳, 加藤 宣之

    日本癌学会総会記事   67回   397 - 397   2008年9月

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  • 異なるHCV(1b型)株由来の全長HCV RNA複製レポーターアッセイ系の開発(Development of genome-length HCV RNA replication reporter assay systems using various genotype 1b HCV strains) 査読

    池田 正徳, 森 京子, 阿部 健一, 西村 剛, 團迫 浩方, 有海 康雄, 中沢 貴秀, 加藤 宣之

    日本癌学会総会記事   67回   482 - 482   2008年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • ATM DNA損傷センサーはC型肝炎ウイルスのRNA複製に必要である(ATM, a DNA damage sensor, is required for hepatitis C virus RNA replication) 査読

    有海 康雄, 黒木 美沙緒, 團迫 浩方, 阿部 健一, 池田 正徳, 脇田 隆字, 加藤 宣之

    日本癌学会総会記事   67回   482 - 483   2008年9月

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  • New efficient replication system with hepatitis C virus genome derived from a patient with acute hepatitis C 査読

    Kyoko Mori, Ken-ichi Abe, Hiromichi Dansako, Yasuo Ariumi, Masanori Ikeda, Nobuyuki Kato

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   371 ( 1 )   104 - 109   2008年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    We report for the first time a new RNA replication system with a hepatitis C virus (HCV) strain (AHI) derived from a patient with acute hepatitis C. Using an HCV replicon RNA library constructed with the AH1 strain (genotype 1b), we first established a cloned cell line, sAH1, harboring the HCV replicon. Cured cells obtained with interferon treatment of sAH1 cells were used for transfection with genome-length HCV RNA possessing four mutations found in sAH1 replicon. Consequently, one cloned cell line, AH1, supporting efficient replication of genome-length HCV RNA was obtained. By the comparison of AH1 cells with the O cells supporting genome-length HCV RNA (HCV-O strain) replication, we found different anti-HCV profiles of interferon-gamma and cyclosporine A between AH1 and O cells. Reporter assay analysis suggests that the diverse effects of interferon-gamma are due to the difference in HCV strains, but not the cellular environment. (c) 2008 Elsevier Inc. All rights reserved

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  • 全長HCV-RNA複製細胞を基に作成したIFN治療後再発モデルによる有効な治療法の検討・評価 査読

    河合 良成, 池田 正徳, 阿部 健一, 矢野 雅彦, 有海 康雄, 團迫 浩方, 加藤 宣之, 山本 和秀

    肝臓   49 ( Suppl.1 )   A172 - A172   2008年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 抗HCV成分・製剤のHCV RNA複製に対する抑制機序におけるMAPK signaling pathwayの関与 査読

    矢野 雅彦, 池田 正徳, 阿部 健一, 有海 康雄, 團迫 浩方, 大越 章吾, 青柳 豊, 加藤 宣之

    肝臓   49 ( Suppl.1 )   A136 - A136   2008年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • DDX3 DEAD-box RNA helicase is required for hepatitis C virus RNA replication 査読

    Yasuo Ariumi, Misao Kuroki, Ken-ichi Abe, Hiromichi Dansako, Masanori Ikeda, Takaji Wakita, Nobuyuki Kato

    JOURNAL OF VIROLOGY   81 ( 24 )   13922 - 13926   2007年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    DDX3, a DEAD-box RNA helicase, binds to the hepatitis C virus (HCV) core protein. However, the role(s) of DDX3 in HCV replication is still not understood. Here we demonstrate that the accumulation of both genome-length HCV RNA (HCV-O, genotype 1b) and its replicon RNA were significantly suppressed in HuH-7-derived cells expressing short hairpin RNA targeted to DDX3 by lentivirus vector transduction. As well, RNA replication of JFH1 (genotype 2a) and release of the core into the culture supernatants were suppressed in DDX3 knockdown cells after inoculation of the cell culture-generated HCVcc. Thus, DDX3 is required for HCV RNA replication.

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  • Limited suppression of the interferon-beta production by hepatitis C virus serine protease in cultured human hepatocytes 査読

    Hiromichi Dansako, Masanori Ikeda, Nobuyuki Kato

    FEBS JOURNAL   274 ( 16 )   4161 - 4176   2007年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    Toll-like receptors and RNA helicase family members [retinoic acid-inducible gene I (RIG-I) and melanoma differentiation associated gene-5 (MDA5)] play important roles in the induction of interferon-P as a major event in innate immune responses after virus infection. TRIF (adaptor protein of Toll-like receptor 3)-mediated and Cardif (adaptor protein of RIG-I or MDA5)-mediated signaling pathways contribute rapid induction of interferon-P through the activation of interferon regulatory factor-3 (IRF-3). Previously, it has been reported that the hepatitis C virus NS3-4A serine protease blocks virus-induced activation of IRF-3 in the human hepatoma cell line HuH-7, and that NS3-4A cleaves TRIF and Cardif molecules, resulting in the interruption of antiviral signaling pathways. On the other hand, it has recently been reported that non-neoplastic human hepatocyte PH5CH8 cells retain robust TRIF- and Cardif-mediated pathways, unlike HuH-7 cells, which lack a TRIF-mediated pathway. In the present study, we further investigated the effect of NS3-4A on antiviral signaling pathways. Although we confirmed that PH5CH8 cells were much more effective than HuH-7 cells for the induction of interferon-P, we obtained the unexpected result that NS3-4A could not suppress the interferon-P production induced by the TRIF-mediated pathway, although it suppressed the Cardif-mediated pathway by cleaving Cardif at the Cys508 residue. Using PH5CH8, HeLa, and HuH-7-derived cells, we further showed that NS3-4A could not cleave TRIF, in disagreement with a previous report describing the cleavage of TRI F by NS3-4A. Taken together, our findings suggest that the blocking of the interferon production by NS3-4A is not sufficient in HCV-Infected hepatocyte cells.

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  • DDX3 DEAD box RNAヘリカーゼはC型肝炎ウイルスのRNA複製に必要である(DDX3 DEAD box RNA helicase is required for hepatitis C virus RNA replication) 査読

    有海 康雄, 黒木 美沙緒, 阿部 健一, 團迫 浩方, 池田 正徳, 脇田 隆字, 加藤 宣之

    日本癌学会総会記事   66回   237 - 237   2007年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 全長HCV RNA複製細胞の長期培養におけるHCVの遺伝的変異動態(HCV genetic variability and dynamics in long-term culture of genome-length HCV RNA replicating cells) 査読

    加藤 宣之, 阿部 健一, 森 京子, 有海 康雄, 團迫 浩方, 池田 正徳

    日本癌学会総会記事   66回   291 - 292   2007年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • Comprehensive analysis of the effects of ordinary nutrients on hepatitis C virus RNA replication in cell culture 査読

    Masahiko Yano, Masanori Ikeda, Ken-ichi Abe, Hiromichi Dansako, Shogo Ohkoshi, Yutaka Aoyagi, Nobuyuki Kato

    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY   51 ( 6 )   2016 - 2027   2007年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    To date, only a limited number of studies have reported finding an influence of ordinary nutrients on hepatitis C virus (HCV) RNA replication. However, the effects of other nutrients on HCV RNA replication remain largely unknown. We recently developed a reporter assay system for genome-length HCV RNA replication in hepatoma-derived HuH-7 cells (OR6). Here, using this OR6 assay system, we comprehensively examined 46 nutrients from four nutrient groups: vitamins, amino acids, fatty acids, and salts. We found that three nutrients-beta-carotene, vitamin D-2, and linoleic acid-inhibited HCV RNA replication and that their combination caused additive and/or synergistic effects on HCV RNA replication. In addition, combined treatment with each of the three nutrients and interferon alpha or beta or fluvastatin inhibited HCV RNA replication in an additive manner, while combined treatment with cyclosporine synergistically inhibited HCV RNA replication. In contrast, we found that vitamin E enhanced HCV RNA replication and negated the effects of the three anti-HCV nutrients and cyclosporine but not those of interferon or fluvastatin. These results will provide useful information for the treatment of chronic hepatitis C patients who also take anti-HCV nutrients as an adjunctive therapy in combination with interferon. In conclusion, among the ordinary nutrients tested, beta-carotene, vitamin D-2, and linoleic acid possessed anti-HCV activity in a cell culture system, and these nutrients are therefore considered to be potential candidates for enhancing the effects of interferon therapy.

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  • Serum-free cell culture system supplemented with lipid-rich albumin for hepatitis C virus (strain O of genotype 1b) replication 査読

    Ken-ichi Abe, Masanori Ikeda, Yasuo Ariumi, Hiromichi Dansako, Nobuyuki Kato

    VIRUS RESEARCH   125 ( 2 )   162 - 168   2007年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    HuH-7 is a highly differentiated hepatoma cell line and the only cell line that supports robust RNA replication of the hepatitis C virus (HCV). HuH-7 cells cause cell death in serum-free culture condition. However, the effect is reversed by supplementation with selenium. Serum-free cell cultures are advantageous for vaccine development and experimental reproducibility. However, HCV RNA replication in HuH-7 cells in serum-free medium had not yet been achieved. Therefore, we tried to develop a system for robust HCV RNA replication in a serum-free cell culture. Although HuH-7 cells grew in serum-free medium in the presence of selenium, HuH-7 cells under these conditions did not support HCV RNA replication in long-term culture. Among the supplements tested, serum-free medium with lipid-rich albumin (LRA) was found to yield robust HCV RNA replication. HCV proteins were detected for more than 9 months in serum-free medium supplemented with LRA. This is the first report to demonstrate a long-term, serum-free cell culture that successfully maintained robust HCV RNA replication. This cell culture system is expected to be a useful tool for vaccine development, as well as for further investigation of cellular factors that are essential for HCV RNA replication. (c) 2007 Elsevier B.V. All rights reserved.

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  • Cell culture-adaptive NS3 mutations required for the robust replication of genome-length hepatitis C virus RNA 査読

    Ken-ichi Abe, Masanori Ikeda, Hiromichi Dansako, Kazuhito Naka, Nobuyuki Kato

    VIRUS RESEARCH   125 ( 1 )   88 - 97   2007年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    We recently established a genome-length HCV RNA-replicating cell line (O strain of genotype 1b; here called O cells) using cured cells derived from sO cells, in which HCV subgenomic replicon RNA with an adaptive NS5A mutation (S2200R) is replicated. Characterization of the O cells revealed a second adaptive NS3 mutation (K1609E) required for genome-length HCV RNA replication. To clarify the role of adaptive mutation in genome-length HCV RNA replication, we newly established one and three kinds of genome-length HCV RNA-replicating cell lines possessing the cell background of so and 0 cells, respectively, and found additional adaptive NS3 mutations (Q11 12R, P1115L, and E1202G) required for the robust replication of genome-length HCV RNA. We further found that specific combinations of adaptive NS3 mutations drastically enhanced HCV RNA replication, regardless of the cell lines examined. These findings suggest that specific viral factors may affect the replication level of genome-length HCV RNA. (c) 2006 Elsevier B.V. All rights reserved.

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  • Tandem repeats of lactoferrin-derived anti-hepatitis C virus peptide enhance antiviral activity in cultured human hepatocytes 査読

    Ken-ichi Abe, Akito Nozaki, Kazushi Tamura, Masanori Ikeda, Kazuhito Naka, Hiromichi Dansako, Hiro-o Hoshino, Katsuaki Tanaka, Nobuyuki Kato

    MICROBIOLOGY AND IMMUNOLOGY   51 ( 1 )   117 - 125   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CENTER ACADEMIC PUBL JAPAN  

    Previously, we found that bovine and human lactoferrin (LF) specifically inhibited hepatitis C virus (HCV) infection in cultured non-neoplastic human hepatocyte-derived PH5CH8 cells, and we identified 33 amino acid residues (termed C-s3-33; amino acid 600-632) from human LF that were primarily responsible for the binding activity to the HCV E2 envelope protein and for the inhibiting activity against HCV infection. Since the anti-HCV activity of C-s3-33 was weaker than that of human LF, we speculated that an increase of E2 protein-binding activity might contribute to the enhancement of anti-HCV activity. To test this possibility, we made two repeats [(C-0-33)(2)] and three repeats [(C-s3-33)(3)] of C-s3-33 and characterized them. Far-Western blot analysis revealed that the E2 protein-binding activities of (C-s3-33), and (C-ws3-33)(3) became stronger than that of the C-0-33, and that the binding activity of (C-s3-33)(3) was stronger than that of (C-s3-33)(3). Using an HCV infection system in PH5CH8 cells, we demonstrated that the anti-HCV activities of (C-s3-33)2 and (C-s3-33)(3) became stronger than that of the C-0-33. Furthermore, using a recently developed infection system with a VSV pseudotype harboring the green fluorescent protein gene and the native E1 and E2 genes, we demonstrated that the antiviral activities of (C-s3-33)(2) and (C-s3-33)(3) were stronger than that of C-s3-33. These results suggest that tandem repeats of LF-derived anti-HCV peptide are useful as anti-HCV reagents.

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  • Different anti-HCV profiles of statins and their potential for combination therapy with interferon 査読

    M Ikeda, K Abe, M Yamada, H Dansako, K Naka, N Kato

    HEPATOLOGY   44 ( 1 )   117 - 125   2006年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOHN WILEY & SONS INC  

    We recently developed a genome-length hepatitis C virus (HCV) RNA replication system (0116) with luciferase as a reporter. The OR6 assay system has enabled prompt and precise quantification of HCV RNA replication. Pegylated interferon (IFN) and ribavirin combination therapy is the world standard for chronic hepatitis Q but its effectiveness is limited to about 55% of patients. Newer therapeutic approaches are needed. In the present study, we used the OR6 assay system to evaluate die anti-HCV activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, called statins, and their effects in combination with IFN-alpha. Five types of statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) were examined for their anti-HCV activities. Fluvastatin exhibited the strongest anti-HCV activity (IC50: 0.9 mu mol/ L), whereas atorvastatin and simvastatin showed moderate inhibitory effects. However, lovastatin, reported recently as an inhibitor of HCV replication, was shown to exhibit the weakest anti-HCV activity. The anti-HCV activities of statins were reversed by the addition of mevalonate or geranylgeraniol. Surprisingly, however, pravastatin exhibited no anti-HCV activity, although it worked as an inhibitor for HMG-CoA reductase. The combination of IFN and the statins (except for pravastatin) exhibited strong inhibitory effects on HCV RNA replication. In combination with IFN, fluvastatin also exhibited a synergistic inhibitory effect. In conclusion, statins, especially fluvastatin, could be potentially useful as new anti-HCV reagents in combination with IFN.

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  • Epigenetic silencing of interferon-inducible genes is implicated in interferon resistance of hepatitis C virus replicon-harboring cells 査読

    K Naka, K Abe, K Takemoto, H Dansako, M Ikeda, K Shimotohno, N Kato

    JOURNAL OF HEPATOLOGY   44 ( 5 )   869 - 878   2006年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Background/Aims: We previously established hepatitis C virus (HCV) replicon-harboring cell lines possessing two interferon (IFN)-resistant phenotypes: a partially resistant phenotype (alpha R series) and a severely resistant phenotype (OR series). We recently found that the severe IFN resistance of the OR-series cells is caused by the functional disruption of type I IFN receptors. Here, we aimed to clarify the mechanism(s) underlying the partial IFN resistance of the alpha R-series cells.
    Methods: alpha R-series cells were pre-treated with 5-azacytidine to evaluate the effects of DNA demethylation on IFN resistance. cDNA microarray analysis was carried out in order to compare 1 alpha R cells, which belong to the alpha R series, treated with both 5-azacytidine and IFN-alpha with cells treated with 5-azacytidine or IFN-alpha alone.
    Results: We found that the IFN-resistant phenotype of alpha R-series cells was impaired by treatment with 5-azacytidine. cDNA microarray analysis identified seven IFN-stimulated genes, which were up-regulated by 5-azacytidine treatment. We demonstrated here that the ectopic expression of each of these seven genes in 1 alpha R cells frequently weakened the IFN resistance of these cells.
    Conclusions: The present results suggest that the epigenetic silencing of IFN-stimulated genes is implicated in the acquisition of a partially IFN-resistant phenotype of HCV replicon-harboring cells. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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  • Hepatitis C virus NS5B delays cell cycle progression by inducing interferon-beta via Toll-like receptor 3 signaling pathway without replicating viral genomes 査読

    K Naka, H Dansako, N Kobayashi, M Ikeda, N Kato

    VIROLOGY   346 ( 2 )   348 - 362   2006年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    To clarify the pathogenesis of hepatitis C virus (HCV), we have studied the effects of HCV proteins using human hepatocytes. Here, we found that HCV NS5B, an RNA-dependent RNA polymerase, delayed cell cycle progression through the S phase in PH5CH8 immortalized human hepatocyte cells. Since treatment with anti-interferon (IFN)-beta neutralizing antibody restored the cell cycle delay, IFN-beta was deemed responsible for the cell cycle delay in NS5B-expressing PH5CH8 cells. The induction of IFN-beta and the cell cycle delay were overridden by the down-regulation of Toll-like receptor 3 (TLR3) through RNA interference in NS5B-expressing PH5CH8 cells. Moreover, the NS5B full form was required for the cell cycle delay, the induction of IFN-beta, and the activation of the IFN-beta signaling pathway. Our findings revealed that NS5B induced IFN-beta through the TLR3 signaling pathway in immortalized human hepatocytes even without replicating viral genomes. (C) 2005 Elsevier Inc. All rights reserved.

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  • Interferon resistance of hepatitis C virus replicon-harbouring cells is caused by functional disruption of type I interferon receptors 査読

    K Naka, K Takemoto, K Abe, H Dansako, M Ikeda, K Shimotohno, N Kato

    JOURNAL OF GENERAL VIROLOGY   86 ( Pt 10 )   2787 - 2792   2005年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SOC GENERAL MICROBIOLOGY  

    Hepatitis C virus (HCV) replicon-harbouring cell lines possessing interferon (IFN)-resistant phenotypes have recently been established. These were divided into two classes: partially IFN resistant and highly IFN resistant. Here, the viral and cellular factors contributing to the IFN resistance of HCV replicon-harbouring cells were evaluated. The results revealed that cellular factors rather than viral factors contributed to a highly IFN-resistant phenotype. The possibility of genetic abnormality of the factors involved in IFN signalling was investigated. As a result, nonsense mutations and deletions in type I IFN receptor genes (IFNAR1 and IFNAR2c) were found in replicon-harbouring cells showing a highly IFN-resistant phenotype, but rarely appeared in cells showing a partially IFN-resistant phenotype. Furthermore, similar genetic alterations were also found in IFN-resistant phenotype, replicon-harbouring cell lines obtained additionally by IFN-beta treatment. Moreover, it was shown that ectopic expression of wild-type IFNAR1 in IFN-resistant phenotype, replicon-harbouring cells possessing the IFNAR1 mutant restored type I IFN signalling.

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  • Hepatitis C virus proteins exhibit conflicting effects on the interferon system in human hepatocyte cells 査読

    H Dansako, K Naka, M Ikeda, N Kato

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   336 ( 2 )   458 - 468   2005年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    We previously found that hepatitis C virus (HCV) core protein (Core) activated the interferon (IFN)-inducible 40/46 kDa 2'-5'-oligoadenylate synthetase (2'-5'-OAS) gene through an IFN-stimulated response element (ISRE) in non-neoplastic human hepatocyte PH5CH8 cells. Here, we found that Core and NS5B synergistically enhanced the 2'-5'-OAS gene promoter activity through ISRE. Further analysis revealed that amino acid positions 12 and/or 13 of Core and RNA-dependent RNA polymerase activity of NS5B were essential for the activation of the 2'-5'-OAS gene promoter. Interestingly, we observed that the activation by Core of NS5B was still partially enhanced by even the NS5B or Core mutant lacking the activating ability, respectively, suggesting an indirect interaction between Core and NS5B. Furthermore, we showed that the activation by NS5B could be explained by NS5B's induction of IFN-P, however, IFN-beta was not induced by Core. Moreover, we showed that the synergistic effect of Core and NS5B was not invalidated by NS3-4A, although NS3-4A significantly inhibited the activation by combination of Core and NS5B. Taken together, our findings reveal that NS5B/Core and NS3-4A exhibit conflicting effects (activation and inhibition) on the IFN system in PH5CH8 cells, and suggest that such effects may promote the distraction of the host defense system to lead to persistent infection. (c) 2005 Elsevier Inc. All rights reserved.

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  • Mizoribine inhibits hepatitis C virus RNA replication: Effect of combination with interferon-alpha 査読

    K Naka, M Ikeda, KI Abe, H Dansako, N Kato

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   330 ( 3 )   871 - 879   2005年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Interferon (IFN)-alpha monotherapy, as well as the more effective combination therapy of IFN-alpha and ribavirin, are currently used for patients with chronic hepatitis C caused by hepatitis C virus (HCV) infection, although the mechanisms of the antiviral effects of these reagents on HCV remain ambiguous, and side effects such as anemia due to the administration of ribavirin present a problem for patients who are advanced in years. Using a recently developed reporter assay system in which genome-length dicistronic HCV RNA encoding Renilla luciferase gene was found to replicate efficiently, we found that mizoribine, an imidazole nucleoside, inhibited HCV RNA replication. The anti-HCV activity of mizoribine (IC50: approximately 100 mu M) was similar to that of ribavirin. Using this genome-length HCV RNA replication monitor system, we were the first to demonstrate that the combination of IFN-alpha and ribavirin exhibited more effective anti-HCV activity than the use of IFN-alpha alone, Moreover, we found that the anti-HCV activity of mizoribine in co-treatment with IFN-alpha was at least equivalent to that of ribavirin. This effect was apparent in the presence of at least 5 mu M mizoribine. Since mizoribine is currently used in several clinical applications and has not been associated with severe side effects, mizoribine is considered to be of potential use as a new anti-HCV reagent in combination with IFN-alpha. (c) 2005 Elsevier Inc. All rights reserved.

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  • Efficient replication of a full-length hepatitis C virus genome, strain O, in cell culture, and development of a luciferase reporter system 査読

    M Ikeda, K Abe, H Dansako, T Nakamura, K Naka, N Kato

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   329 ( 4 )   1350 - 1359   2005年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Recently we reported a subgenomic hepatitis C virus (HCV) replicon derived from HCV (HCV-O strain) infected in non-neoplastic human hepatocyte PH5CH8. In this study, we developed a genome-length dicistronic HCV RNA from HCV-O. A cured HuH-7 cell line (sOc) was obtained from a cloned subgenomic replicon cell line (sO) by interferon (IFN) treatment and used for transfection with genome-length HCV RNA. One cloned cell line, O, was successfully selected by G418 treatment following the introduction of genome-length HCV RNA into sOc cells, and the robust expression of HCV RNA and proteins was confirmed. Oc, a cured cell line, was also obtained from the cloned cell line (O) by IFN treatment. The number of colonies increased drastically when genome-length HCV RNA was introduced into Oc cells. However, the cloned cured cell lines, sOc and Oc, differed in their colony formation efficiency despite their common origin. This result suggests that even a cloned cell line can change its characteristics during cell culture. Sequence analysis of HCV RNA from the O cells revealed an amino acid substitution in the NS3 helicase region (K1609E). This substitution worked as an adaptive mutation in transient reporter and colony formation assays. Using the advantages of this adaptive mutation and of Oc cells in colony formation, we established the first cell line in which genome-length dicistronic HCV RNA encoding a luciferase gene replicated efficiently. This culture system is useful tool for the study of HCV replication and mass screening for anti-HCV reagents. (c) 2005 Elsevier Inc. All rights reserved.

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  • Genetic variation and dynamics of hepatitis C virus replicons in long-term cell culture 査読

    N Kato, T Nakamura, H Dansako, K Namba, K Abe, A Nozaki, K Naka, M Ikeda, K Shimotohno

    JOURNAL OF GENERAL VIROLOGY   86 ( Pt 3 )   645 - 656   2005年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SOC GENERAL MICROBIOLOGY  

    Hepatitis C virus (HCV) genomic sequences are known to vary widely among HCV strains, but to date there have been few reports on the genetic variations and dynamics of HCV in an experimental system of HCV replication. In this study, a genetic analysis of HCV replicons obtained in long-term culture of two HCV replicon cells (50-1 and 1B-2R1), which were established from two HCV strains, 1B-1 and 1B-2, respectively, was performed. One person cultured 50-1 cells for 18 months, and two people independently cultured 50-1 cells for 12 months. 1B-2R1 cells were also cultured for 12 months. The whole nucleotide sequences of the three independent replicon RNA clones obtained at several time points were determined. It was observed that genetic mutations in both replicons accumulated in a time-dependent manner, and that the mutation rates of both replicons were approximately 3.0 x 10(-3) base substitutions/site/year. The genetic diversity of both replicons was also enlarged in a time-dependent manner. The colony formation assay by transfection of total RNAs isolated from both replicon cells at different time points into naive HuH-7 cells revealed that the genetic mutations accumulating with time in both replicons apparently improved colony formation efficiency. Taken together, these results suggest that the HCV replicon system is useful for the analysis of evolutionary dynamics and variations of HCV. Using this replicon cell culture system, it was demonstrated further that neither ribavirin nor its derivative mizoribine accelerated the mutation rate or the increase in the genetic diversity of HCV replicon.

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  • CDNA microarray analysis to compare HCV subgenomic replicon cells with their cured cells 査読

    K Abe, M Ikeda, H Dansako, K Naka, K Shimotohno, N Kato

    VIRUS RESEARCH   107 ( 1 )   73 - 81   2005年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    The hepatitis C virus (HCV) replicon system carrying autonomously replicating HCV subgenomic RNA in human hepatocyte cells is a potent tool for basic studies of HCV, such as viral replication and drug development. Recently, we developed two HCV subgenomic replicons (50-1 and 1B-2R1) derived from two HCV strains, 1B-1 and 1B-2, respectively. Since the expression of HCV proteins is thought to affect the host cells' gene expression profiles, we attempted to identify target genes of HCV proteins using microarray analysis (9970 genes) by comparing 50-1 and 1B-2R1 replicon cells with their "cured cells", from which the replicons had been eliminated by prolonged treatment with interferon-a. The results showed that HCV replicons could have a variety of expression profiles in human hepatocytes. The results also showed that 2 and 6 genes were commonly up-regulated (more than 2.0-fold) and down-regulated (less than 0.50-fold), respectively in both 50-1 and 1B-2R1 replicon cells compared with their cured cells. The differential expression profiles of genes selected by the microarray analysis Were confirmed with standard RT-PCR and real-time LightCycler PCR. It was noteworthy that the commonly down-regulated genes contained large multifunctional proteases 2 and 7, which are known as catalytic subunits of immunoproteasome. and serine proteinase inhibitor clade C. Our microarray analysis demonstrated that HCV subgenomic replicons can change the gene expression profiles of host and it allowed us to compile the first list of genes that the replicons transcriptionally regulate. (C) 2004 Elsevier B.V. All rights reserved.

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  • cDNA microarray analysis of lactoferrin expression in non-neoplastic human hepatocyte PH5CH8 cells. 査読

    Tamura T, Nozaki A, Abe K, Dansako H, Naka K, Ikeda M, Tanaka K, Kato N

    Biochimica et biophysica acta   1721 ( 1-3 )   73 - 80   2005年1月

  • cDNA microarray analysis of lactoferrin expression in non-neoplastic human hepatocyte PH5CH8 cells 査読

    T Tamura, A Nozaki, K Abe, H Dansako, K Naka, M Ikeda, K Tanaka, N Kato

    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS   1721 ( 1-3 )   73 - 80   2005年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Lactoferrin (LF), a milk protein belonging to the iron transporter transferrin family, is known as a primary defense protein against pathogenic microorganisms. Previously, we found that bovine and human LFs prevented hepatitis C virus infection in cultured human hepatocytes by a direct interaction with the virus. Since LF is proposed to have transcriptional regulatory activity in addition to its antimicrobial function, we sought to identify the target genes that these two types of LF have in common. To this end, we were the first to perform microarray analysis (9970 genes) using human hepatocytes that expressed bovine or human LF by retrovirus-mediated gene transfer. In the results, LF could give a variety of expression profiles in the human hepatocytes, and showed that 9 and 19 genes were commonly upregulated (more than 2.0-fold) and down-regulated (less than 0.50-fold), respectively, in both bovine and human LF-expressing cells compared with control cells. Among these genes, we found that gamma-aminobutyric acid (GABA)-B receptor 2 was transcriptionally down-regulated by bovine and human Us, but not by human transferrin. Furthermore, we obtained the suggestive result that LF may modulate the level of intracellular cAMP. This modulation is one of the cellular responses that the GABA-B receptor modifies. This is the first report of microarray analysis applied to search inclusively for the target genes of LF. (C) 2004 Elsevier B.V. All rights reserved.

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  • Establishment of hepatitis C virus replicon cell lines possessing interferon-resistant phenotype 査読

    K Namba, K Naka, H Dansako, A Nozaki, M Ikeda, Y Shiratori, K Shimotohno, N Kato

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   323 ( 1 )   299 - 309   2004年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    To clarify the mechanism underlying resistance to interferon (IFN) by the hepatitis C virus (HCV) in patients with chronic hepatitis, we attempted to develop an IFN-resistant HCV replicon from the IFN-sensitive 50-1 replicon established previously. By treating 50-1 replicon cells with a prolonged low-dose treatment of IFN-alpha and then transfecting the total RNA derived from the IFN-alpha-treated replicon cells, we successfully obtained four clones (named 1, 3, 4, and 5) of HCV replicon cells that survived against IFN-alpha (200 IU/ml). These cloned cells were further treated with IFN-alpha or IFN-beta (increased gradually to 2000 or 1000 IU/ml, respectively). This led to four replicon cell lines (alphaR series) possessing the IFN-alpha-resistant phenotype and four replicon cell lines (PR series) possessing the IFN-beta-resistant phenotype. Furthermore, we obtained an additional replicon cell line (alphaRmix) possessing the IFN-alpha-resistant phenotype by two rounds of prolonged treatment with IFN-alpha and RNA transfection as mentioned above. Characterization of these obtained HCV replicon cell lines revealed that the PR series were highly resistant to both IFN-alpha and IFN-beta, although the alphaR series containing alphaRmix were only partially resistant to both IFN-alpha and IFN-beta. Genetic analysis of these HCV replicons found one common amino acid substitution in the NS4B and several additional amino acid substitutions in the NS5A of the PR series, suggesting that these genetic alterations are involved in the IFN resistance of these HCV replicons. These newly established HCV replicon cell lines possessing IFN-resistant phenotypes are the first useful tools for understanding the mechanisms by which HCV acquires IFN resistance in vivo. (C) 2004 Elsevier Inc. All rights reserved.

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  • Promotion of microsatellite instability by hepatitis C virus core protein in human non-neoplastic hepatocyte cells 査読

    A Naganuma, H Dansako, T Nakamura, A Nozaki, N Kato

    CANCER RESEARCH   64 ( 4 )   1307 - 1314   2004年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    Hepatitis C virus proteins exert an effect on a variety of cellular functions, including gene expression, signal transduction, and apoptosis, and because they possess oncogenic potentials, they have also been suggested to play an important role in hepatocarcinogenesis. Although the mechanisms of hepatocarcinogenesis remain poorly understood, we hypothesized that the disease may arise because of a disturbance of the DNA repair system by hepatitis C virus proteins. To test this hypothesis, we developed a reproducible microsatellite instability assay system for mismatch-repair using human-cultured cells transducted with pCXpur retrovirus expression vector, in which the puromycin resistance gene was rendered out-of-frame by insertion of a (CA)(17) dinucleotide repeat tract immediately following the ATG start codon. Using several human cancer cell lines known to be replication error positive or negative, we demonstrated that this assay system was useful for monitoring the propensity for mismatch-repair in the cells. This assay system was applicable to nonneoplastic human PH5CH8 hepatocytes, which could support hepatitis C virus replication. Using PH5CH8 cells, in which hepatitis C virus proteins were stably expressed by the retrovirus-mediated gene transfer, we found that the core protein promoted microsatellite instability in PH5CH8 cells. Interestingly, such promotion by the core protein only occurred in cells having the core protein belonging to genotype 1b or 2a and did not occur in cells having the core protein belonging to genotype 1a, 2b, or 3a. This is the first report to demonstrate that the core protein may disturb the DNA repair system.

    DOI: 10.1158/0008-5472.CAN-03-2992

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  • Differential activation of interferon-inducible genes by hepatitis C virus core protein mediated by the interferon stimulated response element 査読

    H Dansako, A Naganuma, T Nakamura, F Ikeda, A Nozaki, N Kato

    VIRUS RESEARCH   97 ( 1 )   17 - 30   2003年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    We previously found that hepatitis C virus (HCV) core protein, which possesses the consensus sequence of genotype 1b, transcriptionally activates the interferon (IFN)-inducible 2'-5'-oligoadenylate synthetase (2'-5'-OAS) gene in human hepatocyte cells. To clarify the mechanism of this activation, we further characterized the core protein as an activator of the 2'-5'-OAS gene. We demonstrated that the activation of the 2'-5'-OAS gene by the core protein is a general phenomenon, regardless of HCV genotype and strain. We showed that the 20 N-terminal amino acids (aa) of the core protein were important to the activation of the 2'-5'-OAS gene, although this N-terminal region did not have any effect on the subcellular localization of the core protein. We demonstrated that the core protein was able to activate all promoters possessing the IFN-stimulated response element (ISRE) examined. However, we found that the level of activation of the 2'-5'-OAS gene promoter possessing a particular variant type of ISRE was significantly higher than that of other IFN-inducible gene promoters. This phenomenon was confirmed using synthetic promoters possessing five repeats of the consensus or a 2'-5'-OAS-type ISRE. In addition, we showed that gene activation induced by the core protein is mediated by the ISRE. These results imply that the core protein prefers a subclass of IFN-inducible genes, the promoters of which possess the 2-5'-OAS-type ISRE. Accordingly, we found that the IFN-inducible double-stranded RNA-specific adenosine deaminase gene promoter, possessing a 2'-5'-OAS-type ISRE sequence, was also efficiently activated by the core protein. The exact mechanism by which the core protein enhances gene expression was not determined, but we could find no effects of core protein on gene expression and phosphorylation status of the components of the JAK-STAT signaling transduction pathway. (C) 2003 Elsevier B.V. All rights reserved.

    DOI: 10.1016/S0168-1702(03)00218-1

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  • Establishment of a hepatitis C virus subgenomic replicon derived from human hepatocytes infected in vitro 査読

    N Kato, K Sugiyama, K Namba, H Dansako, T Nakamura, M Takami, K Naka, A Nozaki, K Shimotohno

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   306 ( 3 )   756 - 766   2003年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    The hepatitis C virus (HCV) replicon system is a potent tool for understanding the mechanisms of HCV replication and proliferation, and for the development of treatments for patients with HCV. Recently, we established an HCV subgenomic replicon (501) using HCV genome RNA obtained from the cultured human T cell line MT-2C infected with HCV (isolate 1B-1) in vitro. In order to further obtain other HCV replicons without difficulty, we generated a replicon RNA library derived from human non-neoplastic hepatocytes infected with HCV (isolate 1B-2) in vitro. Upon transfection of the generated RNA library to "cured cells," from which the 50-1 subgenomic replicon was eliminated by prolonged treatment with interferon-alpha, we successfully established a new HCV subgenomic replicon, 1B-2R1. We characterized 1B-2R1 replicon in terms of efficiency of replication, HCV sequence, and sensitivity to interferons. The results revealed that the replication level of the 1B-2R1 replicon was comparable to that of the 50-1 replicon. We also found that the 1B-2R1 replicon possessed an HCV sequence distinct from those of other replicons established to date, and that the 1B-2R1 replicon was sensitive to interferon-a, interferon-P, and interferon-gamma. Taken together, present results indicate that the replicon RNA library generated using an in vitro HCV infection system is useful for the establishment of an HCV subgenomic replicon. (C) 2003 Elsevier Science (USA). All rights reserved.

    DOI: 10.1016/S0006-291X(03)01047-7

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  • A novel fusion variant of the MORF and CBP genes detected in therapy-related myelodysplastic syndrome with t(10;16)(q22;p13) 査読

    K Kojima, K Kaneda, C Yoshida, H Dansako, N Fujii, T Yano, K Shinagawa, M Yasukawa, S Fujita, M Tanimoto

    BRITISH JOURNAL OF HAEMATOLOGY   120 ( 2 )   271 - 273   2003年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING LTD  

    We report a case of therapy-related myelodysplastic syndrome (t-MDS) with t(10;16)(q22;p13), in which novel fusion transcripts of the MORF and CBP genes were detected. In one MORF-CBP fusion transcript, exon 15 of the MORF gene was fused in frame with exon 5 of the CBP gene. In a reciprocal CBP-MORF transcript, exon 4 of the CBP gene was fused in frame with exon 16 of the MORF gene. This is the first reported case of t-MDS associated with t(10;16), and provides molecular evidence that the novel MORF-CBP and/or CBP-MORF fusion protein(s) might play an important role in the development of t-MDS.

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  • Specificity of polymerase chain reaction-based clonality analysis of immunoglobulin heavy chain gene rearrangement for the detection of bone marrow infiltrate in B-cell lymphoma-associated haemophagocytic syndrome 査読

    K Kojima, K Kaneda, M Yasukawa, K Tanaka, T Inoue, T Yamashita, H Dansako, ST Sakugawa, T Kozuka, M Hara, M Tanimoto

    BRITISH JOURNAL OF HAEMATOLOGY   119 ( 3 )   616 - 621   2002年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING LTD  

    As a wide range of disorders underlie haemophagocytic syndrome, a rapid distinction between benign polyclonal and malignant monoclonal lymphoid proliferations is critical. We investigated whether polymerase chain reaction ( PCR) amplification of immunoglobulin heavy chain gene rearrangement could efficiently detect clonal B-cell populations in non-diagnostic marrow for B-cell lymphoma-associated haemophagocytic syndrome (B-LAHS). On amplifying two DNA samples per biopsy, no reproducible monoclonal PCR result was found in reactive haemophagocytic marrows. In contrast, four out of nine assessable B-LAHS patients with histomorphologically and immunohistochemically lymphoma-free bone marrow showed a reproducible monoclonal immunoglobulin heavy chain gene rearrangement. At the molecular level, two B-LAHS patients had lymphoma-free marrow as demonstrated by patient-specific PCR, suggesting that haemophagocytic marrow is not always associated with lymphoma involvement. PCR-based demonstration of clonal B-cell populations in marrow would add an extra dimension to B-LAHS diagnosis.

    DOI: 10.1046/j.1365-2141.2002.03866.x

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  • Therapy-related myelodysplastic syndrome/acute myeloid leukemia M2 and translocation (8;21) 査読

    M Sakugawa, K Kojima, K Kaneda, K Masuda, H Dansako, K Shinagawa, F Ishimaru, K Ikeda, K Niiya, M Harada, M Tanimoto

    ANNALS OF HEMATOLOGY   80 ( 12 )   763 - 766   2001年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER-VERLAG  

    An 80-year-old woman developed therapy-related myelodysplastic syndrome with translocation (8;21), which was successfully treated with an acute myeloid leukemia oriented chemotherapy. Five years before admission she had received cyclophosphamide, epirubicin, and carboplatin for endometrial cancer. The leukemia cell morphology alerted us to the possibility of the presence of t(8;21) before cytogenetic results were obtained, and AML1/ETO fusion transcript was detected by reverse transcription polymerase chain reaction. She achieved complete remission after one course of idarubicin and cytosine arabinoside. She has remained in complete remission for 6 months. Our experience suggests that recognition of typical morphological features for de novo M2 acute myeloid leukemia with t(8;21) would be important in diagnosis of therapy related myelodysplastic syndrome/acute myeloid leukemia with this translocation, which could respond to an intensive chemotherapy.

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  • Molecular characterization of the ERGIC-53 gene in two Japanese patients with combined factor V-factor VIII deficiency 査読

    H. Dansako, F. Ishimaru, Y. Takai, J. Tomoda, K. Nakase, K. Fujii, Y. Ogama, T. Kozuka, N. Sezaki, K. Honda, M. Harada

    Annals of Hematology   80 ( 5 )   292 - 294   2001年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Combined deficiency of factor V and factor VIII is a distinct clinical entity and is an autosomal recessive disorder. Recently identification of the gene, the endoplasmic reticulum-Golgi intermediate compartment (ERGIC-53), responsible for combined factor V-factor VIII deficiency and mutations of the ERGIC-53 gene in affected patients have been reported. In this report we analyzed two Japanese patients with combined factor V-factor VIII deficiency by genomic polymerase chain reaction and sequencing analysis. In one patient we found a point mutation of C to T at nucleotide 604 in exon 5, resulting in a transition of arginine to stop codon, which was reported in previous reports. The DdeI digestion study demonstrated that this patient is homozygous for this nonsense mutation. In the other patient we found no mutation in the ERGIC-53 gene in analysis of the entire coding region and the intron/exon junctions, which is also consistent with the previous reports, suggesting the possibility of defects at other genetic loci.

    DOI: 10.1007/s002770000283

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  • Two novel gene mutations in type I antithrombin deficiency 査読

    Kenji Niiya, Toru Kiguchi, Hiromichi Dansako, Kingo Fujimura, Takahiro Fujimoto, Kenji Iijima, Mitsune Tanimoto, Mine Harada

    International Journal of Hematology   74 ( 4 )   469 - 472   2001年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Carden Jennings Publishing Co. Ltd  

    We studied the molecular basis of type I antithrombin (AT) deficiency in 2 Japanese families, in which affected persons had histories of recurrent venous thrombosis and low (about 50% of normal) levels of AT protein according to measurements by both functional and antigen assays. Southern blotting of DNA isolated from peripheral leukocytes revealed no abnormalities in all the cases examined. Direct sequencing of the polymerase chain reaction (PCR) products from case 1 suggested a novel heterozygous nonsense mutation in exon 4 (GAG→TAG at nucleotide position 7627, leading to Glu306 stop). The sequencing of the subclones of the patient's exon 4 products confirmed the nonsense mutation. No other sequence abnormalities were detected in the rest of the PCR products. The same mutation was detected in this patient's brother, who had a history of recurrent venous thrombosis and a reduced level of AT activity. In case 2, the direct sequencing of PCR products suggested a novel heterozygous 9-bp deletion in exon 3a(-CACTTC at nucleotide position 5354-5362, leading to the deletion of 3 amino acids, His120, Phe121, and Phe122). The 9-bp deletion mutation in the region of a unique quasi palindrome was confirmed by sequencing several of the subclones of the patient's exon 3a from the PCR products. No other mutations were found by direct sequencing of the rest of the coding regions. The 2 mutations found in this study are novel. The use of PCR and the sequencing of the PCR product subclones has simplified and confirmed the detection and characterization of the various AT muta-tions. © 2001 The Japanese Society of Hematology.

    DOI: 10.1007/BF02982095

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  • Additional translocation (8;21)(q22;q22) in a patient with Philadelphia-positive chronic myelogenous leukaemia in the blastic phase 査読

    K Kojima, M Yasukawa, F Ishimaru, H Dansako, Y Matsuo, Y Kimura, Y Nawa, M Hara, M Harada

    BRITISH JOURNAL OF HAEMATOLOGY   106 ( 3 )   720 - 722   1999年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL SCIENCE LTD  

    We report a case of Philadelphia-positive chronic myelogenous leukaemia in blastic phase with the additional translocation (8:21)(q22;q22), which is frequent in acute myeloid leukaemia but not in chronic myelogenous leukaemia. The t(8;21) was not detected in the chronic phase, and was the only additional chromosomal anomaly in the blastic clone. Reverse transcription-polymerase chain reaction revealed the AML1/ETO fusion transcript in the cells of blastic phase but not in those of chronic phase. Regarding t(9:22). the breakpoint on chromosome 22 occurred in the CL-BCR region of the BCR gene, resulting in hybrid BCR/ABL mRNA with an e19a2 junction. Our findings provided molecular evidence that t(8;21) can occur as an additional genetic change in Philadelphia-positive chronic myelogenous leukaemia.

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  • Molecular characterization of total kininogen deficiency in Japanese patients 査読

    Fumihiko Ishimaru, Hiromichi Dansako, Koichi Nakase, Nobuharu Fujii, Nobuo Sezaki, Hiroyuki Nakayama, Norihiko Fujii, Yutaka Komiyama, Kenji Iijima, Katsuto Takenaka, Takanori Teshima, Katsuji Shinagawa, Kazuma Ikeda, Kenji Niiya, Mine Harada

    International Journal of Hematology   69 ( 2 )   126 - 128   1999年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Kininogens are multifunctional plasma glycoproteins. There are two forms of human kininogen: low molecular weight kininogen (LK) and high molecular weight kininogen (HK). Both are derived from the same gene by alternative splicing. Some patients with kininogen deficiency have been reported to be deficient only in HK while others are deficient in both HK and LK (total kininogen deficiency). We analyzed three Japanese patients with total kininogen deficiency by the Csp45I digestion study of exon 5 as previously reported in Williams trait and found that two had the same point mutation of C to T at base 22 of exon 5, resulting in a transition of CGA (Are) codon to TGA (Stop) codon.This is the first report of molecular characterization of total kininogen deficiency in the Japanese population. © 1999 The Japanese Society of Hematology.

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▼全件表示

書籍等出版物

  • 生命科学のためのウイルス学 : 感染と宿主応答のしくみ, 医療への応用

    Harper, D. R. (David R.), 下遠野, 邦忠, 瀬谷, 司( 担当: 共訳 ,  範囲: 第9章 ウイルス、ベクターとゲノム学)

    南江堂  2015年2月  ( ISBN:9784524268375

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    総ページ数:xii, 332p   記述言語:日本語

    CiNii Books

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  • 日本臨牀 73巻 2号

    ( 担当: 分担執筆 ,  範囲: C型肝炎ウイルス感染の認識機構)

    日本臨牀社  2015年 

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  • 臨牀消化器内科6月増刊号 C型肝炎のすべて

    ( 担当: 分担執筆 ,  範囲: HCV持続感染のしくみ)

    2014年 

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  • 肝疾患Review 2006-2007

    ( 担当: 分担執筆 ,  範囲: インターフェロンによるHCVの増殖制御)

    2006年 

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MISC

  • OXIDATIVE STRESS INDUCES ANTI-HCV STATUS VIA THE ACTIVATION OF MEK-ERK1/2 SIGNALING PATHWAY

    Masahiko Yano, Masanori Ikeda, Ken-ichi Abe, Yoshinari Kawai, Misao Kuroki, Kyoko Mori, Hiromichi Dansako, Yasuo Ariumi, Yasunobu Matsuda, Shougo Ohkoshi, Yutaka Aoyagi, Nobuyuki Kato

    HEPATOLOGY   50 ( 4 )   965A - 965A   2009年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JOHN WILEY & SONS INC  

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  • C型肝炎ウイルスエンベロープ蛋白質に結合するラクトフェリン由来ペプチドの同定とその感染防御

    阿部 健一, 野崎 昭人, 田村 一志, 池田 正徳, 仲 一仁, 中村 孝志, 團迫 浩方, 星野 洪郎, 田中 克明, 加藤 宣之

    Milk Scinece   53:348-353   2004年

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  • Dominant negative isoform of the Ikaros gene in patients with adult B-cell acute lymphoblastic leukemia

    K Nakase, F Ishimaru, N Avitahl, H Dansako, K Matsuo, K Fujii, N Sezaki, H Nakayama, T Yano, S Fukuda, K Imajoh, M Takeuchi, A Miyata, M Hara, M Yasukawa, Takahashi, I, H Taguchi, K Matsue, S Nakao, Y Niho, K Takenaka, K Shinagawa, K Ikeda, K Niiya, M Harada

    CANCER RESEARCH   60 ( 15 )   4062 - 4065   2000年8月

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    記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    Gene targeting studies in mice have shown that the transcription factor Ikaros plays an essential role in lymphoid development and as a tumor suppressor in T cells, whereas the related gene Aiolos functions as a tumor suppressor in B cells. We analyzed the expression levels of the Ikaros gene family, Ikaros and Aiolos, in human bone marrow samples from patients with adult acute lymphoblastic leukemia [ALL (n = 46; B-cell ALL = 41; T-cell ALL = 5)]. Overexpression of the dominant negative isoform of Ikaros gene Ik-6 was observed in 14 of 41 B-cell ALL patients by reverse transcription-PCR, and the results were confirmed by sequencing analysis and immunoblotting, None of the other dominant negative isoforms of the Ikaros gene were detected by reverse transcription-PCR analysis, Southern blotting analysis with PstI digestion revealed that those patients with the dominant negative isoform Ik-6 might have small mutations in the Ikaros locus. We did not detect any overexpression of dominant negative isoforms of Aiolos in adult ALL patients. These results suggest that Ikaros plays a key role in human B-cell malignancies through the dominant negative Isoform Ik-6.

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講演・口頭発表等

  • B型肝炎ウイルスによるChk2キナーゼの活性化は細胞外小胞がミトコンドリアDNAを細胞間伝達することにより起こる

    團迫浩方, 上田優輝, 佐藤伸哉, 加藤宣之

    第7回 日本細胞外小胞学会 

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    開催年月日: 2020年10月26日 - 2020年10月27日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • A new hepatoma cell line exhibiting high susceptibility to HBV infection.

    Ueda Y, Gu W, Dansako H, Nishitsuji H, Satoh S, Shimotohno K, Kato N

    第67回日本ウイルス学会学術集会 

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    開催年月日: 2019年10月29日 - 2019年10月31日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • HBV-triggered antiviral signaling is transduced to neighboring cells by mediating extracellular vesicles in human immortalized hepatocyte NKNT-3

    Dansako H, Imai H, Ueda Y, Satoh S, Kato N

    第67回日本ウイルス学会学術集会 

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    開催年月日: 2019年10月29日 - 2019年10月31日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • 細胞外小胞はB型肝炎ウイルス感染が誘導する自然免疫応答を細胞間で伝達する

    團迫浩方, 今井大誉, 上田優輝, 佐藤伸哉, 加藤宣之

    第6回 日本細胞外小胞学会 

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    開催年月日: 2019年10月24日 - 2019年10月25日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • A new human hepatoma cell line exhibiting high susceptibility to HBV infection.

    Youki Ueda,Hiromichi Dansako,Shinya Satoh,Kunitada Shimotohno,Nobuyuki Kato

    2019 International HBV Meeting 

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    開催年月日: 2019年10月1日 - 2019年10月5日

    記述言語:英語   会議種別:ポスター発表  

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  • ヒト不死化肝NKNT-3細胞において、細胞外小胞を介する細胞間自然免疫伝達機構の解明

    團迫浩方, 今井大誉, 上田優輝, 佐藤伸哉, 加藤宣之

    第34回中国四国ウイルス研究会 

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    開催年月日: 2019年6月29日 - 2019年6月30日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • HBV高感受性新規肝がん細胞株の樹立

    上田優輝, 谷?琳, 團迫浩方, 西辻裕紀, 佐藤伸哉, 下遠野邦忠, 加藤宣之

    第34回中国四国ウイルス研究会 

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    開催年月日: 2019年6月29日 - 2019年6月30日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • Highly expression of STING restricts HBV infection by mediating the induction of type III interferon in human immortalized hepatocyte NKNT-3

    Dansako H, Imai H, Ueda Y, Satoh S, Shimotohno K, Kato N

    第66回日本ウイルス学会学術集会 

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    開催年月日: 2018年10月28日 - 2018年10月30日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • Screening of the new host factors necessary for HBV proliferation using plural human cell lines

    Ueda Y, Dansako H, Satoh S, Shimotohno K, Kato N

    第66回日本ウイルス学会学術集会 

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    開催年月日: 2018年10月28日 - 2018年10月30日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • Mechanism of GPAM suppression by anti-HCV drug ribavirin

    Onomura D, Satoh S, Ueda Y, Dansako H, Kato N

    第66回日本ウイルス学会学術集会 

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    開催年月日: 2018年10月28日 - 2018年10月30日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • Analysis of host and viral factors contributing to resistant acquision for the preclinical anti-HCV drugs, N-89 and N-251

    Gu W, Ueda Y, Satoh S, Dansako H, Kato N

    第66回日本ウイルス学会学術集会 

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    開催年月日: 2018年10月28日 - 2018年10月30日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • Topoisomerase II inhibitor triggers cyclic GMP-AMP synthase-dependent innate immune response in human immortalized hepatocyte NKNT-3

    Imai H, Dansako H, Ueda Y, Satoh S, Kato N

    第66回日本ウイルス学会学術集会 

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    開催年月日: 2018年10月28日 - 2018年10月30日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • Drug screening for suppression of lipogenesis through downregulation of C/EBP-alpha

    Satoh S, Onomura D, Watashi K, Ueda Y, Dansako H, Honda M, Kaneko S, Kato N

    第66回日本ウイルス学会学術集会 

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    開催年月日: 2018年10月28日 - 2018年10月30日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • Screening of the new host factors necessary for HBV proliferation using plural human cell lines.

    Youki Ueda,Hiromichi Dansako,Shinya Satoh,Kunitada Shimotohno,Nobuyuki Kato

    2018 International HBV Meeting 

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    開催年月日: 2018年10月3日 - 2018年10月6日

    記述言語:英語   会議種別:ポスター発表  

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  • Analysis of proteins within exosomes secreted from hepatitis B virus-infected human immortalized hepatocyte NKNT-3

    Dansako H, Imai H, Ueda Y, Satoh S, Kato N

    第10回日本RNAi研究会・第5回日本細胞外小胞学会 

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    開催年月日: 2018年8月29日 - 2018年8月31日

    記述言語:英語   会議種別:ポスター発表  

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  • 抗HCV薬として開発中のN-89とN-251に対する抵抗性の獲得に寄与する宿主側とウイルス側因子の解析

    谷?琳, 上田優輝, 佐藤伸哉, 團迫浩方, 加藤宣之

    第33回中国四国ウイルス研究会 

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    開催年月日: 2018年6月23日 - 2018年6月24日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 抗HCV薬リバビリンによる中性脂肪合成抑制機序の解明

    佐藤伸哉, 小野村大地, 上田優輝, 團迫浩方, 加藤宣之

    第33回中国四国ウイルス研究会 

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    開催年月日: 2018年6月23日 - 2018年6月24日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • ヒト不死化肝NKNT-3細胞におけるtopoisomerase II阻害剤によるcGAS依存的な自然免疫応答の誘導

    今井大誉, 團迫浩方, 上田優輝, 佐藤伸哉, 加藤宣之

    第33回中国四国ウイルス研究会 

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    開催年月日: 2018年6月23日 - 2018年6月24日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • HCV以外の広範なウイルスにも有効性を示した抗マラリア薬候補N-89とN-251

    上田優輝, 谷?琳, 團迫浩方, 佐藤伸哉, 池田正徳, 加藤宣之

    第33回中国四国ウイルス研究会 

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    開催年月日: 2018年6月23日 - 2018年6月24日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 抗HCV薬リバビリンによるGPAM発現抑制機序の解明

    小野村大地, 佐藤伸哉, 上田優輝, 團迫浩方, 加藤宣之

    第33回中国四国ウイルス研究会 

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    開催年月日: 2018年6月23日 - 2018年6月24日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • The cGas-STING signaling pathway is required for both the innate immune response against HBV and the suppression of HBV assembly

    Hiromichi Dansako,Youki Ueda,Nobuaki Okumura,Shinya Satoh,Masaya Sugiyama,Masashi Mizokami,Masanori Ikeda,Nobuyuki Kato

    第63回 日本ウイルス学会学術集会 

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    開催年月日: 2015年11月22日 - 2015年11月24日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • cGAS-STINGシグナル経路はB型肝炎ウイルスの感染と会合を制御する

    團迫 浩方、上田 優輝、奥村 暢章、佐藤 伸哉、杉山 真也、溝上 雅史、池田 正徳、加藤 宣之

    第30回 中国四国ウイルス研究会 

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    開催年月日: 2015年6月27日 - 2015年6月28日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • B型肝炎ウイルスの細胞内複製の認識に重要なシグナル経路の解明

    團迫 浩方、佐藤 伸哉、溝上 雅史、池田 正徳、加藤 宣之

    第62回日本ウイルス学会学術集会 

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    開催年月日: 2014年11月10日 - 2014年11月12日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • Human Hepatoma HuH-7 Cell Line-derived RSc cells Show Higher Viral Productivity in Response to Infection with HCV-JFH-1 than Huh7.5 Cells

    Hiromichi Dansako,Hiroki Hiramoto,Masanori Ikeda,Takaji Wakita,Nobuyuki Kato

    21st International Symposium on Hapatitis C and Related Viruses 

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    開催年月日: 2014年9月7日 - 2014年9月11日

    記述言語:英語   会議種別:ポスター発表  

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  • B型肝炎ウイルスの細胞内複製を認識する宿主因子の探索

    團迫 浩方、佐藤 伸哉、溝上 雅史、池田 正徳、加藤 宣之

    中国四国ウイルス研究会 

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    開催年月日: 2014年6月28日 - 2014年6月29日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:山口大学  

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  • 骨粗鬆症治療剤ラロキシフェンはC型肝炎ウイルスの増殖を抑制する

    武田 緑、池田 正徳、森 京子、矢野 雅彦、有海 康雄、團迫 浩方、脇田 隆字、加藤 宣之

    第36回 日本分子生物学会 

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    開催年月日: 2013年12月3日 - 2013年12月6日

    記述言語:日本語   会議種別:ポスター発表  

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  • HBV持続感染培養系の確立に向けたヒト肝細胞株のHBV複製能の解析

    奥村 暢章、池田 正徳、武田 緑、佐藤 伸哉、團迫 浩方、溝上 雅史、加藤 宣之

    第36回 日本分子生物学会 

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    開催年月日: 2013年12月3日 - 2013年12月6日

    記述言語:日本語   会議種別:ポスター発表  

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  • 抗HCV活性を有する中国由来の漢方薬であるサナギタケ(北冬虫夏草)

    上田 優輝、森 京子、佐藤 伸哉、團迫 浩方、池田 正徳、加藤 宣之

    第61回日本ウイルス学会学術集会 

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    開催年月日: 2013年11月10日 - 2013年11月12日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • C型肝炎ウイルスのゲノム複製が2年間にわたることで発現レベルが変動したマイクロRNAの同定

    瀬島 寛恵、森 京子、佐藤 伸哉、團迫 浩方、池田 正徳、加藤 宣之

    第61回日本ウイルス学会学術集会 

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    開催年月日: 2013年11月10日 - 2013年11月12日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • Rab18はC型肝炎ウイルスの感染性粒子形成に重要な宿主因子である

    團迫浩方 他

    第61回日本ウイルス学会学術集会 

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    開催年月日: 2013年11月10日 - 2013年11月12日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • ヒト肝細胞株におけるHBV複製能の評価

    奥村 暢章、池田 正徳、武田 緑、佐藤 伸哉、團迫 浩方、溝上 雅史、加藤 宣之

    第61回日本ウイルス学会学術集会 

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    開催年月日: 2013年11月10日 - 2013年11月12日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • C型肝炎ウイルスのライフサイクルにおける宿主因子annexinA1の役割

    平本 洸貴、團迫 浩方、瀬島 寛恵、森 京子、佐藤 伸哉、池田 正徳、脇田 隆字、加藤 宣之之

    第61回日本ウイルス学会学術集会 

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    開催年月日: 2013年11月10日 - 2013年11月12日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • リバビリン耐性全長HCV-RNA複製細胞株の樹立

    佐藤 伸哉、森 京子、上田 優輝、瀬島 寛恵、團迫 浩方、池田 正徳、加藤 宣之

    第61回日本ウイルス学会学術集会 

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    開催年月日: 2013年11月10日 - 2013年11月12日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • HBV複製系の開発に向けた肝細胞株の選択

    奥村 暢章、池田 正徳、武田 緑、團迫 浩方、加藤 宣之

    第22回 日本消化器関連学会週間 

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    開催年月日: 2013年10月9日 - 2013年10月10日

    記述言語:日本語   会議種別:ポスター発表  

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  • Identification of two microRNAs showing decreased expression in cell-based HCV RNA replication for 2years

    Hiroe Sejima,Kyoko Mori,Shinya Satoh,Hiromichi Dansako,Masanori Ikeda,Nobuyuki Kato

    20th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2013年10月6日 - 2013年10月10日

    記述言語:英語   会議種別:ポスター発表  

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  • Raloxifene inhibits hepatitis C virus infection and replication

    Midori Takeda,Masanori Ikeda,Kyoko Mori,Masahiko Yano,Yasuo Ariumi,Hiromichi Dansako,Takaji Wakita,Nobuyuki Kato

    20th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2013年10月6日 - 2013年10月10日

    記述言語:英語   会議種別:ポスター発表  

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  • Rab18 is required for viral assembly of hepatitis C virus through the association with core protein around lipid droplet.

    Hiromichi Dansako他

    20th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2013年10月6日 - 2013年10月10日

    記述言語:英語   会議種別:ポスター発表  

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  • Establishment of hepatitis C virus RNA replicating cell lines possessing ribavirin-resistant phenotypes

    Shinya Satoh,Kyoko Mori,Hiromichi Dansako,Masanori Ikeda,Nobuyuki Kato

    20th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2013年10月6日 - 2013年10月10日

    記述言語:英語   会議種別:ポスター発表  

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  • Anti-HCV activity of Cordyceps militaris used as a chinese herbal medicine

    Youki Ueda,Kyoko Mori,Shinya Satoh,Hiromichi Dansako,Masanori Ikeda,Nobuyuki Kato

    20th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2013年10月6日 - 2013年10月10日

    記述言語:英語   会議種別:ポスター発表  

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  • Identification of microRNAs showing differential expression profiles in cell-based HCV RNA replication for 2years

    瀬島 寛恵、森 京子、佐藤 伸哉、團迫 浩方、池田 正徳、加藤 宣之

    第72回日本癌学会学術集会 

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    開催年月日: 2013年10月3日 - 2013年10月5日

    記述言語:日本語   会議種別:ポスター発表  

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  • 骨粗鬆症治療剤であるラロキシフェンは抗HCV活性を示す

    武田 緑、池田 正徳、森 京子、矢野 雅彦、有海 康雄、團迫 浩方、脇田 隆字、加藤 宣之

    第28回中国四国ウイルス研究会 

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    開催年月日: 2013年6月22日 - 2013年6月23日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 肝細胞株におけるHBV複製能の評価

    奥村 暢章、池田 正徳、武田 緑、佐藤 伸哉、團迫 浩方、加藤 宣之

    第28回中国四国ウイルス研究会 

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    開催年月日: 2013年6月22日 - 2013年6月23日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • B型肝炎ウイルスの自然免疫応答モデルの構築

    團迫浩方 他

    第28回中国四国ウイルス研究会 

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    開催年月日: 2013年6月22日 - 2013年6月23日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • C型肝炎ウイルスの感染性ウイルス粒子産生に対するannexin A1の影響

    平本 洸貴、團迫 浩方、瀬島 寛恵、佐藤 伸哉、池田 正徳、加藤 宣之

    第28回中国四国ウイルス研究会 

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    開催年月日: 2013年6月22日 - 2013年6月23日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 2年間にわたるC型肝炎ウイルスのゲノム複製によって発現レベルに変動をきたしたmicroRNAの同定

    瀬島 寛恵、森 京子、團迫 浩方、池田 正徳、加藤 宣之

    第28回中国四国ウイルス研究会 

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    開催年月日: 2013年6月22日 - 2013年6月23日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 中国由来の漢方薬であるサナギタケ(北冬虫夏草)が有する抗HCV活性

    上田 優輝、森 京子、團迫 浩方、池田 正徳、加藤 宣之

    第28回中国四国ウイルス研究会 

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    開催年月日: 2013年6月22日 - 2013年6月23日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 中国由来の漢方薬であるサナギタケ(北冬虫夏草)に見出された抗HCV活性

    上田 優輝、森 京子、團迫 浩方、池田 正徳、加藤 宣之

    第49回日本肝臓学会総会 

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    開催年月日: 2013年6月6日 - 2013年6月7日

    記述言語:日本語   会議種別:ポスター発表  

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  • 骨粗鬆症治療剤であるラロキシフェンの抗HCV活性機構について

    武田 緑、池田 正徳、森 京子、矢野 雅彦、有海 康雄、團迫 浩方、脇田 隆字、加藤 宣之

    第49回日本肝臓学会総会 

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    開催年月日: 2013年6月6日 - 2013年6月7日

    記述言語:日本語   会議種別:口頭発表(基調)  

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  • C型肝炎ウイルスの複製環境に関わるmicroRNAの探索

    瀬島 寛恵、森 京子、團迫 浩方、池田 正徳、加藤 宣之

    第49回日本肝臓学会総会 

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    開催年月日: 2013年6月6日 - 2013年6月7日

    記述言語:日本語   会議種別:ポスター発表  

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  • 酸化ストレスを介して強い抗HCV活性を示す抗マラリア薬として開発中の化合物

    上田 優輝、森 京子、團迫 浩方、金 惠淑、綿矢 有祐、池田 正徳、加藤 宣之

    第60回日本ウイルス学会学術集会 

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    開催年月日: 2012年11月13日 - 2012年11月15日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • リバビリンに対する感受性を決定する宿主因子の同定とその因子の病態進行への関与について

    森 京子、本多 政夫、池田 正徳、團迫 浩方、金子 周一、加藤 宣之

    第60回日本ウイルス学会学術集会 

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    開催年月日: 2012年11月13日 - 2012年11月15日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • Potent anti-HCV activities found in preclinical anti-malarial drugs is promptly exerted through oxidative stress

    Youki Ueda,Kyoko Mori,Hiromichi Dansako,Hye-Sook Kim,Yusuke Wataya,Masanori Ikeda,Nobuyuki Kato

    19th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2012年10月5日 - 2012年10月9日

    記述言語:英語   会議種別:ポスター発表  

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  • Multidirectional analysis for a host factor determining the anti-HCV activity of ribavirin

    Kyoko Mori,Masao Honda,Masanori Ikeda,Hiromichi Dansako,Shuichi Kaneko,Nobuyuki Kato

    19th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2012年10月5日 - 2012年10月9日

    記述言語:英語   会議種別:ポスター発表  

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  • Multifaceted analysis for a host factor determining the anti-HCV activity of ribavirin

    Kyoko Mori,Masao Honda,Masanori Ikeda,Hiromichi Dansako,Shuichi Kaneko,Nobuyuki Kato

    第71回日本癌学会学術総会 

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    開催年月日: 2012年9月19日 - 2012年9月21日

    記述言語:英語   会議種別:ポスター発表  

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  • Potent anti-HCV activities found in preclinical anti-malarial drugs

    Youki Ueda,Kyoko Mori,Hiromichi Dansako,Hye-Sook Kim,Yusuke Wataya,Masanori Ikeda,Nobuyuki Kato

    第71回日本癌学会学術総会 

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    開催年月日: 2012年9月19日 - 2012年9月21日

    記述言語:英語   会議種別:ポスター発表  

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  • クラスAスカベンジャー受容体によるC型肝炎ウイルスの新規感染認識機構の解明

    團迫 浩方、山根 大典、加藤 宣之、Stanley.M.Lemon

    第27回中国四国ウイルス研究会 

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    開催年月日: 2012年6月23日 - 2012年6月24日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • HCV production requires the PML tumor suppressor protein

    Misao Kuroki,Yasuo Ariumi,Masanori Ikeda,Hiromichi Dansako,Takaji Wakita,Nobuyuki Kato

    18th INTERNATIONAL SYMPOSIUM ON HEPATITIS C VIRUS AND RELATED VIRUSES 

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    開催年月日: 2011年9月8日 - 2011年9月12日

    記述言語:英語   会議種別:ポスター発表  

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  • IL28B領域のSNPが異なる肝細胞株(HuH7,Li23)における抗HCV剤の感受性

    池田 正徳、森 京子、武田 緑、中澤 貴秀、有海 康雄、團迫 浩方、加藤 宣之

    第33回日本分子生物学会年会 

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    開催年月日: 2010年12月7日 - 2010年12月10日

    記述言語:日本語   会議種別:ポスター発表  

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  • リバビリンの抗HCV活性を決定する因子の解析

    森 京子、池田 正徳、有海 康雄、團迫 浩方、脇田 隆字、加藤 宣之

    第58回日本ウイルス学会学術集会 

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    開催年月日: 2010年11月7日 - 2010年11月9日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 異なるHCV株、細胞株を用いたHCV RNA複製培養細胞での薬剤評価

    池田 正徳、森 京子、武田 緑、中澤 貴秀、有海 康雄、團迫 浩方、加藤 宣之

    第58回日本ウイルス学会学術集会 

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    開催年月日: 2010年11月7日 - 2010年11月9日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • がん抑制因子PMLはC型肝炎ウイルスのライフサイクルに必須である

    黒木 美沙緒、有海 康雄、池田 正徳、團迫 浩方、脇田 隆字、加藤 宣之

    第58回日本ウイルス学会学術集会 

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    開催年月日: 2010年11月7日 - 2010年11月9日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • ヒト肝癌細胞株Li23由来の新しいHCV-RNA複製システムを用いたリバビリンの作用機序の解明

    森 京子、池田 正徳、有海 康雄、團迫 浩方、加藤 宣之

    第14回日本肝臓学会大会 

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    開催年月日: 2010年10月13日

    記述言語:日本語   会議種別:ポスター発表  

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  • C型肝炎ウイルスに対する新しい抗ウイルス剤スクリーニング系の開発

    池田 正徳、森 京子、中澤 貴秀、有海 康雄、團迫 浩方、加藤 宣之

    第14回日本肝臓学会大会 

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    開催年月日: 2010年10月13日

    記述言語:日本語   会議種別:ポスター発表  

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  • Mechanism of anti-HCV of ribavirin in a novel HCV replication cell system

    森 京子、池田 正徳、有海 康雄、團迫 浩方、加藤 宣之

    第69回日本癌学会学術総会 

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    開催年月日: 2010年9月22日 - 2010年9月24日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • The PML tumor suppressor protein is required for HCV life

    黒木 美沙緒、有海 康雄、池田 正徳、團迫 浩方、脇田 隆字、加藤 宣之

    第69回日本癌学会学術総会 

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    開催年月日: 2010年9月22日 - 2010年9月24日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • Development of genome-length HCV RNA replication assay systems derived from different HCV strains using HuH-7 and Li23 cells

    Masanori Ikeda,Kyoko Mori,Takahide Nakazawa,Yasuo Ariumi,Hiromichi Dansako,Nobuyuki Kato

    C型肝炎ウイルス及び関連するウイルスに関する国際会議 

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    開催年月日: 2010年9月10日 - 2010年9月14日

    記述言語:英語   会議種別:ポスター発表  

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  • Anti-HCV mechanism of ribavirin in novel HCV replication cell systems

    Kyoko Mori,Masanori Ikeda,Yasuo Ariumi,Hiromichi Dansako,Takaji Wakita,Nobuyuki Kato,

    C型肝炎ウイルス及び関連するウイルスに関する国際会議 

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    開催年月日: 2010年9月10日 - 2010年9月14日

    記述言語:英語   会議種別:ポスター発表  

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  • Li23細胞由来のHCV-RNA複製システムを用いたリバビリンの抗HCV機構の解析

    森 京子、池田 正徳、有海 康雄、團迫 浩方、加藤 宣之

    中国四国ウイルス研究会 

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    開催年月日: 2010年6月26日 - 2010年6月27日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • がん抑制因子PMLはC型肝炎ウイルスの生活環に必要である

    黒木 美沙緒、有海 康雄、池田 正徳、團迫 浩方、脇田 隆字、加藤 宣之

    中国四国ウイルス研究会 

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    開催年月日: 2010年6月26日 - 2010年6月27日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 癌抑制因子PMLはHCV粒子産生に必要である

    黒木 美沙緒、有海 康雄、池田 正徳、團迫 浩方、脇田 隆字、加藤 宣之

    第57回日本ウイルス学会学術集会 

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    開催年月日: 2009年10月25日 - 2009年10月27日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • オンコスタチンMはインターフェロンの抗HCV活性を相乗的に増強する

    池田 正徳、森 京子、有海 康雄、團迫 浩方、加藤 宣之

    第57回日本ウイルス学会学術集会 

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    開催年月日: 2009年10月25日 - 2009年10月27日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • リバビリンの抗HCV活性を解析評価できるLi23細胞由来のHCV-RNA複製システム

    森 京子、池田 正徳、有海 康雄、團迫 浩方、加藤 宣之

    第57回日本ウイルス学会学術集会 

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    開催年月日: 2009年10月25日 - 2009年10月27日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • ESCRT小胞輸送系のHCV産生への関与

    有海 康雄、黒木 美沙緒、牧 正敏、池田 正徳、團迫 浩方、脇田 隆字、加藤 宣之

    第57回日本ウイルス学会学術集会 

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    開催年月日: 2009年10月25日 - 2009年10月27日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 抗潰瘍剤によるC型慢性肝炎の新たな治療戦略-TeprenoneはStatinのゲラニルゲラニル化阻害を増強しHCV複製抑制効果を増強する-

    河合 良成、池田 正徳、矢野 雅彦、阿部 健一、西村 剛、團迫 浩方、有海 康雄、脇田 隆字、山本 和秀、加藤 宣之

    第57回日本ウイルス学会学術集会 

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    開催年月日: 2009年10月25日 - 2009年10月27日

    記述言語:日本語   会議種別:ポスター発表  

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  • HCVコア蛋白質のアミノ酸の違いとIFN応答性との関係についての培養細胞を用いた解析

    池田 房雄、團迫 浩方、西村 剛、河合 良成、有海 康雄、池田 正徳、高木 章乃夫、岩崎 良章、加藤 宣之、山本 和秀

    第13回日本肝臓学会大会 

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    開催年月日: 2009年10月14日 - 2009年10月16日

    記述言語:日本語   会議種別:ポスター発表  

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  • The ESCRT pathway is required for HCV production.

    Yasuo Ariumi, Misao Kuroki, Masatoshi Maki, Masanori Ikeda, Hiromichi Dansako, Takaji Wakita, and Nobuyuki Kato.

    第16回C型肝炎ウイルス及び関連するウイルスに関する国際会議 

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    開催年月日: 2009年10月3日 - 2009年10月7日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • Replicons from genotype 1b HCV-positive sera exhibit diverse sensitivities to anti-HCV reagents.

    Go Nishimura, Masanori Ikeda, Kyoko Mori, Takahide Takazawa, Yasuo Ariumi,Hiromichi Dansako, and Nobuyuki Kato.

    第16回C型肝炎ウイルス及び関連するウイルスに関する国際会議 

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    開催年月日: 2009年10月3日 - 2009年10月7日

    記述言語:英語   会議種別:ポスター発表  

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  • The PML tumor suppressor protein is required for HCV production.

    Misao Kuroki, Yasuo Ariumi, Masanori Ikeda, Hiromichi Dansako, Takaji Wakita, and Nobuyuki Kato.

    第16回C型肝炎ウイルス及び関連するウイルスに関する国際会議 

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    開催年月日: 2009年10月3日 - 2009年10月7日

    記述言語:英語   会議種別:ポスター発表  

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  • Involvement of the MEK-ERK1/2 Signaling Pathway in the Anti-HCV Mechanism of Oxidative Stress.

    Masahiko Yano, Masanori Ikeda, Ken-ichi Abe, Yoshinari Kawai, Misao Kuroki,Kyoko Mori, Hiromichi Dansako, Yasuo Ariumi, Yasunobu Matsuda, Shougo Ohkoshi,Yutaka Aoyagi, and Nobuyuki Kato.

    第16回C型肝炎ウイルス及び関連するウイルスに関する国際会議 

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    開催年月日: 2009年10月3日 - 2009年10月7日

    記述言語:英語   会議種別:ポスター発表  

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  • Li23 cell-derived HCV-RNA replicating systems enabling analysis for anti-HCV mechanism of ribavirin.

    Kyoko Mori, Masanori Ikeda, Yasuo Ariumi, Hiromichi Dansako, and Nobuyuki Kato.

    第16回C型肝炎ウイルス及び関連するウイルスに関する国際会議 

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    開催年月日: 2009年10月3日 - 2009年10月7日

    記述言語:英語   会議種別:ポスター発表  

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  • Anti-ulcer agent, teprenone, enhanced statin’s anti-HCV activity by augmenting theinhibition of geranylgeranylation.

    Yoshinari Kawai, Masanori Ikeda, Masahiko Yano, Ken-ichi Abe, Go Nishimura,Hiromichi Dansako, Yasuo Ariumi, Takaji Wakita, Kazuhide Yamamoto, and Nobuyuki Kato.

    第16回C型肝炎ウイルス及び関連するウイルスに関する国際会議 

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    開催年月日: 2009年10月3日 - 2009年10月7日

    記述言語:英語   会議種別:ポスター発表  

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  • Oncostatin M synergistically inhibits HCV RNA replication in combination with interferon-a.

    Masanori Ikeda, Kyoko Mori, Yasuo Ariumi, Hiromichi Dansako, and Nobuyuki Kato.

    第16回C型肝炎ウイルス及び関連するウイルスに関する国際会議 

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    開催年月日: 2009年10月3日 - 2009年10月7日

    記述言語:英語   会議種別:ポスター発表  

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  • 抗潰瘍剤によるC型慢性肝炎の新たな治療戦略-Teprenone(Selbex?)とPlaunotol(Kelnac?)のHCV複製抑制効果-

    河合 良成、池田 正徳、森 京子、阿部 健一、矢野 雅彦、池田 房雄、有海 康雄、團迫 浩方、山本 和秀、加藤 宣之

    第24回中国四国ウイルス研究会 

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    開催年月日: 2009年7月4日 - 2009年7月5日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 亜ヒ酸は酸化ストレスとグルタチオンレドックスシステムを介してC型肝炎ウイルス(HCV)RNA複製を抑制する

    黒木 美沙緒、有海 康雄、池田 正徳、團迫 浩方、脇田 隆字、加藤 宣之

    第24回中国四国ウイルス研究会 

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    開催年月日: 2009年7月4日 - 2009年7月5日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • C型急性肝炎患者由来の全長HCV-RNA複製細胞株の樹立とその応用

    森 京子、阿部 健一、團迫 浩方、有海 康雄、池田 正徳、加藤 宣之

    第24回中国四国ウイルス研究会 

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    開催年月日: 2009年7月4日 - 2009年7月5日

    記述言語:日本語   会議種別:口頭発表(一般)  

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  • 抗潰瘍剤によるC型慢性肝炎の新たな治療戦略-Teprenone(Selbex?)とPlaunotol(Kelnac?)のHCV複製抑制効果-

    河合 良成、池田 正徳、森 京子、阿部 健一、矢野 雅彦、池田 房雄、有海 康雄、團迫 浩方、山本 和秀、加藤 宣之

    第45回日本肝臓学会総会 

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    開催年月日: 2009年6月4日 - 2009年6月5日

    記述言語:日本語   会議種別:ポスター発表  

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  • 日常的に摂取し抗HCV効果を有する栄養成分の全長HCV RNA複製細胞を用いた網羅的探索

    矢野雅彦、池田正徳、阿部健一、*團迫浩方、大越章吾、青柳 豊、加藤宣之

    第55回日本ウイルス学会学術集会・総会 

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    開催年月日: 2007年10月21日 - 2007年10月23日

    会議種別:ポスター発表  

    開催地:札幌市  

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  • HCVのRNA複製に必要な宿主因子DDX3 DEAD box RNAへリカーゼ。

    有海康雄、黒木美沙緒、阿部健一、*團迫浩方、池田正徳、脇田隆字、加藤宣之

    第55回日本ウイルス学会学術集会・総会 

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    開催年月日: 2007年10月21日 - 2007年10月23日

    会議種別:口頭発表(一般)  

    開催地:札幌市  

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  • DNA損傷センサーATMとChk2はHCVのRNA複製に必要な宿主因子である。

    有海康雄、黒木美沙緒、阿部健一、*團迫浩方、池田正徳、脇田隆字、トロノ ディディエ、加藤宣之

    第55回日本ウイルス学会学術集会・総会 

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    開催年月日: 2007年10月21日 - 2007年10月23日

    会議種別:口頭発表(一般)  

    開催地:札幌市  

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  • C型急性肝炎患者由来の1b型HCVレプリコン複製細胞株の樹立

    森 京子、阿部健一、*團迫浩方、有海康雄、池田正徳、加藤宣之

    第55回日本ウイルス学会学術集会・総会 

     詳細を見る

    開催年月日: 2007年10月21日 - 2007年10月23日

    会議種別:ポスター発表  

    開催地:札幌市  

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  • 全長HCV-RNAの複製レベルを指標として生細胞のままアッセイできる新しい抗ウイルス剤評価システム

    *團迫浩方、池田正徳、阿部健一、森 京子、有海康雄、加藤宣之

    第55回日本ウイルス学会学術集会・総会 

     詳細を見る

    開催年月日: 2007年10月21日 - 2007年10月23日

    会議種別:口頭発表(一般)  

    開催地:札幌市  

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  • 全長HCV-RNA複製細胞の長期培養に生じるHCVの遺伝的多様性

    加藤宣之、阿部健一、森 京子、有海康雄、*團迫浩方、池田正徳

    第55回日本ウイルス学会学術集会・総会 

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    開催年月日: 2007年10月21日 - 2007年10月23日

    会議種別:ポスター発表  

    開催地:札幌市  

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  • HCV genetic variation and dynamics in long-term culture of genome-length HCV RNA replication cells.

    Nobuyuki Kato, Ken-ichi Abe, Kyoko Mori, Yasuo Ariumi, *Hiromichi Dansako, Masanori Ikeda

    第66回日本癌学会総会 

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    開催年月日: 2007年10月3日 - 2007年10月5日

    会議種別:ポスター発表  

    開催地:横浜市  

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  • DDX3 DEAD box RNA helicase is required for hepatitis C virus RNA replication.

    Yasuo Ariumi, Misao Kuroki, Ken-ichi Abe, *Hiromichi Dansako, Masanori Ikeda, Takaji Wakita, Nobuyuki Kato

    第66回日本癌学会総会 

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    開催年月日: 2007年10月3日 - 2007年10月5日

    会議種別:口頭発表(一般)  

    開催地:横浜市  

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  • Comprehensive screening of ordinary nutrients expected to enhance the effects of anti-HCV reagents.

    Masanori Ikeda, Masahiko Yano, Ken-ichi Abe, *Hiromichi Dansako, Shogo Ohkoshi, Yutaka Aoyagi, Nobuyuki Kato

    第66回日本癌学会総会 

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    開催年月日: 2007年10月3日 - 2007年10月5日

    会議種別:口頭発表(一般)  

    開催地:横浜市  

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  • HCV genetic variability and dynamics in long-term culture of genome-length HCV RNA-replicating cells.

    Nobuyuki Kato, Ken-ichi Abe, Kyoko Mori, Yasuo Ariumi, *Hiromichi Dansako, Masanori Ikeda

    14 th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2007年9月9日 - 2007年9月13日

    会議種別:ポスター発表  

    開催地:Glasgow, Scotland UK  

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  • DNA damage sensors, ATM and Chk2, are required for hepatitis C virus RNA replication.

    Yasuo Ariumi, Misao Kuroki, Ken-ichi Abe, *Hiromichi Dansako, Masanori Ikeda, Takaji Wakita, Didier Trono, Nobuyuki Kato

    14 th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2007年9月9日 - 2007年9月13日

    会議種別:ポスター発表  

    開催地:Glasgow, Scotland UK  

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  • Serum-free cell culture system supplemented with lipid-rich albumin for genome-length HCV RNA replication.

    Ken-ichi Abe, Masanori Ikeda, Yasuo Ariumi, *Hiromichi Dansako, Nobuyuki Kato

    14 th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2007年9月9日 - 2007年9月13日

    会議種別:ポスター発表  

    開催地:Glasgow, Scotland UK  

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  • Comprehensive analysis of the ordinary nutrients as the novel partners of anti-HCV reagents.

    Masahiko Yano, Masanori Ikeda, Ken-ichi Abe, *Hiromichi Dansako, Shogo Ohkoshi, Yutaka Aoyagi, Nobuyuki Kato

    14 th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2007年9月9日 - 2007年9月13日

    会議種別:ポスター発表  

    開催地:Glasgow, Scotland UK  

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  • A new antiviral assay system using living cells harboring genome-length HCV RNA.

    *Hiromichi Dansako, Masanori Ikeda, Ken-ichi Abe, Kyoko Mori, Yasuo Ariumi, Nobuyuki Kato

    14 th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2007年9月9日 - 2007年9月13日

    会議種別:ポスター発表  

    開催地:Glasgow, Scotland UK  

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  • Limited suppression of the interferon-β production by hepatitis C virus serine protease in cultured human hepatocytes.

    *Hiromichi Dansako, Masanori Ikeda, Nobuyuki Kato

    第72回日本インターフェロン・サイトカイン学会学術集会 

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    開催年月日: 2007年7月5日 - 2007年7月6日

    会議種別:ポスター発表  

    開催地:京都市  

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  • 持続的な全長HCV RNA複製を維持できる無血清培地を用いた細胞培養系の開発

    阿部健一,池田正徳,有海康雄,*團迫浩方,加藤宣之

    第23回中国四国ウイルス研究会 

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    開催年月日: 2007年6月16日 - 2007年6月17日

    会議種別:口頭発表(一般)  

    開催地:松山市  

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  • C型急性肝炎患者血清由来のHCV 1bレプリコン複製細胞株の樹立

    森 京子,阿部健一,*團迫浩方,有海康雄,池田正徳,加藤宣之

    第23回中国四国ウイルス研究会 

     詳細を見る

    開催年月日: 2007年6月16日 - 2007年6月17日

    会議種別:口頭発表(一般)  

    開催地:松山市  

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  • 全長HCV RNAの複製に影響を与える日常的に摂取する栄養成分の同定および評価

    矢野雅彦,池田正徳,阿部健一,*團迫浩方,大越章吾,青柳豊,加藤宣之

    第23回中国四国ウイルス研究会 

     詳細を見る

    開催年月日: 2007年6月16日 - 2007年6月17日

    会議種別:口頭発表(一般)  

    開催地:松山市  

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  • 抗HCV剤治療効果の増強が期待される物質の網羅的スクリーニング-C型肝炎に対する治療戦略の最大化を目指して-.

    矢野雅彦,池田正徳,阿部健一,*團迫浩方,大越章吾,青柳豊,加藤宣之

    第43回日本肝臓学会総会 

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    開催年月日: 2007年5月31日 - 2007年6月1日

    会議種別:口頭発表(一般)  

    開催地:東京  

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  • ヒト肝癌由来の培養細胞におけるC型肝炎ウイルスおよびエタノールのTGF-β産生に及ぼす影響に関する解析

    山田将士,池田正徳,阿部健一,*團迫浩方,加藤宣之

    第54回日本ウイルス学会学術集会・総会 

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    開催年月日: 2006年11月19日 - 2006年11月21日

    開催地:名古屋市  

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  • C型肝炎ウイルスNS3-4A蛋白質のインターフェロン-β産生阻害メカニズム

    * 團迫浩方,池田正徳,加藤宣之

    第54回日本ウイルス学会学術集会・総会 

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    開催年月日: 2006年11月19日 - 2006年11月21日

    開催地:名古屋市  

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  • 全長HCV RNAの効率的な複製を引き起こすNS3領域の適応変異に関する解析

    阿部健一,池田正徳,*團迫浩方,加藤宣之

    第54回日本ウイルス学会学術集会・総会 

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    開催年月日: 2006年11月19日 - 2006年11月21日

    開催地:名古屋市  

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  • 1b型と2a型HCVのシスエレメント領域のキメラウイルスを用いたウイルスの複製および粒子産生に関する解析

    池田正徳,阿部健一,*團迫浩方,脇田隆宇,加藤宣之

    第54回日本ウイルス学会学術集会・総会 

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    開催年月日: 2006年11月19日 - 2006年11月21日

    開催地:名古屋市  

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  • 全長HCV RNAの複製を長期間維持できる無血清培地を用いた細胞培養系の開発

    阿部健一,池田正徳,*團迫浩方,加藤宣之

    第54回日本ウイルス学会学術集会・総会 

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    開催年月日: 2006年11月19日 - 2006年11月21日

    開催地:名古屋市  

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  • HCV RNAの複製を生細胞のまま観察できる培養システムの開発

    *團迫浩方,池田正徳,阿部健一,加藤宣之

    第54回日本ウイルス学会学術集会・総会 

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    開催年月日: 2006年11月19日 - 2006年11月21日

    開催地:名古屋市  

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  • HCV-O (1b) とJFH1 (2a) のシスエレメントキメラウイルスの作成とそれらを用いたHCV複製効率規定領域の解析

    池田正徳,阿部健一,*團迫浩方,脇田隆宇,加藤宣之

    第65回日本癌学会総会 

     詳細を見る

    開催年月日: 2006年9月28日 - 2006年9月30日

    開催地:横浜市  

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  • HCV RNAの複製レベルを生細胞のまま定量できる新しい評価システムの開発

    *團迫浩方,池田正徳,阿部健一,加藤宣之

    第65回日本癌学会総会 

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    開催年月日: 2006年9月28日 - 2006年9月30日

    開催地:横浜市  

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  • HCV RNAの複製を著しく亢進させる適応変異の組合せの同定

    阿部健一,池田正徳,*團迫浩方,仲 一仁,加藤宣之

    第65回日本癌学会総会 

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    開催年月日: 2006年9月28日 - 2006年9月30日

    開催地:横浜市  

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  • Comparative analysis of inhibiting activities against IFN-beta production of NS3-4As derived from patients with different hepatic conditions.

    *Hiromichi Dansako, Kazunori Takemoto, Kazuhito Naka, Masanori Ikeda, Nobuyuki Kato

    13 th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2006年8月27日 - 2006年8月31日

    開催地:Cairns, Australia  

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  • Development of a new cell-based assay for monitoring HCV RNA replication level with living cells.

    *Hiromichi Dansako, Masanori Ikeda, Ken-ichi Abe, Nobuyuki Kato

    13 th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2006年8月27日 - 2006年8月31日

    開催地:Cairns, Australia  

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  • Tandem repeats of lactoferrin-derived anti-HCV peptide enhance the antiviral activity.

    Ken-ichi Abe, Akito Nozaki, Kazushi Tamura, Masanori Ikeda, Kazuhito Naka, *Hiromichi Dansako, Hiro-o Hoshino, Nobuyuki Kato

    13 th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2006年8月27日 - 2006年8月31日

    開催地:Cairns, Australia  

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  • Combination of cell culture-adaptivemutations causes the drastic enhancement of genome-length HCV RNA replication.

    Ken-ichi Abe, Masanori Ikeda, *Hiromichi Dansako, Kazuhito Naka, Nobuyuki Kato

    13 th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2006年8月27日 - 2006年8月31日

    開催地:Cairns, Australia  

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  • Production and characterization of infectious HCVs from JFH1 (2a) with cis-element of HCV-O (1b).

    Masanori Ikeda, Ken-ichi Abe, *Hiromichi Dansako, Takaji Wakita, Nobuyuki Kato

    13 th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2006年8月27日 - 2006年8月31日

    開催地:Cairns, Australia  

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  • 全長HCV RNAの効率的な複製を引き起こす適応変異に関する解析

    阿部健一,池田正徳,*團迫浩方,仲 一仁,加藤宣之

    第22回中国四国ウイルス研究会 

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    開催年月日: 2006年6月10日 - 2006年6月11日

    開催地:鳥取市  

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  • 生細胞のままHCV RNA複製を観察できるシステムの開発

    *團迫浩方,池田正徳,阿部健一,加藤宣之

    第22回中国四国ウイルス研究会 

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    開催年月日: 2006年6月10日 - 2006年6月11日

    開催地:鳥取市  

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  • C型肝炎ウイルスおよびエタノールのTGF-b産生に及ぼす影響について

    山田将士,池田正徳,阿部健一,*團迫浩方,加藤宣之

    第22回中国四国ウイルス研究会 

     詳細を見る

    開催年月日: 2006年6月10日 - 2006年6月11日

    開催地:鳥取市  

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  • C型肝炎ウイルスレプリコン細胞のインターフェロン抵抗性獲得機構

    加藤宣之,阿部健一,竹本和憲,*團迫浩方,池田正徳,下遠野邦忠

    第53回日本ウイルス学会学術集会・総会 

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    開催年月日: 2005年11月20日 - 2005年11月22日

    開催地:横浜市  

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  • C型肝炎ウイルス蛋白質のインターフェロン-β産生系に対する相反的効果

    *團迫浩方,池田正徳,加藤宣之

    第53回日本ウイルス学会学術集会・総会 

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    開催年月日: 2005年11月20日 - 2005年11月22日

    開催地:横浜市  

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  • 全長HCV RNA複製抑制効果を示すスタチンの種類による抗HCV効果の違いとインターフェロンとの併用による相乗的抗HCV効果

    池田正徳,阿部健一,山田将士,*團迫浩方,加藤宣之

    第53回日本ウイルス学会学術集会・総会 

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    開催年月日: 2005年11月20日 - 2005年11月22日

    開催地:横浜市  

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  • 各種病態由来のC型肝炎ウイルスNS3-4A: IFN-β産生抑制効果の比較

    竹本和憲,*團迫浩方,池田正徳,加藤宣之

    第53回日本ウイルス学会学術集会・総会 

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    開催年月日: 2005年11月20日 - 2005年11月22日

    開催地:横浜市  

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  • HCV-O株由来の全長HCV RNA複製細胞群の樹立と適応変異に関する解析

    阿部健一,池田正徳,*團迫浩方,加藤宣之

    第53回日本ウイルス学会学術集会・総会 

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    開催年月日: 2005年11月20日 - 2005年11月22日

    開催地:横浜市  

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  • HCV proteins exhibit contradictory effects on interferon system in human hepatocyte cells.

    *Hiromichi Dansako, Kazuhito Naka, Masanori Ikeda, Nobuyuki Kato

    12 th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2005年10月2日 - 2005年10月6日

    開催地:Montreal, Canada  

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  • HMG-CoA reductase inhibitors as a new class of anti-HCV reagents: their different effects on HCV replication and their applications for combination therapy with IFN.

    Masanori Ikeda, Ken-ichi Abe, Masashi Yamada, *Hiromichi Dansako, Kazuhito Naka, Nobuyuki Kato

    12 th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2005年10月2日 - 2005年10月6日

    開催地:Montreal, Canada  

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  • Identification of a cell culture-adaptive mutation in newly established genome-length HCV RNA replicating cell lines.

    Ken-ichi Abe, Masanori Ikeda, *Hiromichi Dansako, Kazuhito Naka, Nobuyuki Kato

    12 th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2005年10月2日 - 2005年10月6日

    開催地:Montreal, Canada  

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  • Interferon resistance of HCV replicons is caused by functional disruption of type I interferon receptors.

    Kazuhito Naka, Kazunori Takemoto, Ken-ichi Abe, *Hiromichi Dansako, Masanori Ikeda, Kunitada Shimotohno, Nobuyuki Kato

    12 th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2005年10月2日 - 2005年10月6日

    開催地:Montreal, Canada  

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  • 全長HCV RNAレポーター評価システムにより見出したスタチンとインターフェロンの併用による相乗的抗ウイルス効果

    池田正徳,阿部健一,*團迫浩方,仲 一仁,加藤宣之

    第64回日本癌学会総会 

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    開催年月日: 2005年9月14日 - 2005年9月16日

    開催地:札幌市  

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  • HCV-O株由来の全長HCV RNA複製細胞群の樹立

    阿部健一,池田正徳,*團迫浩方,仲 一仁,加藤宣之

    第64回日本癌学会総会 

     詳細を見る

    開催年月日: 2005年9月14日 - 2005年9月16日

    開催地:札幌市  

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  • 各種病態由来のHCV NS3-4A: それらの遺伝子解析とIFN-b産生抑制効果の比較

    竹本和憲,仲 一仁,*團迫浩方,池田正徳,加藤宣之

    第21回中国四国ウイルス研究会 

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    開催年月日: 2005年6月18日 - 2005年6月19日

    開催地:岡山県倉敷市  

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  • HCV-O株由来の全長HCV RNA複製細胞群の樹立

    阿部健一,池田正徳,*團迫浩方,仲 一仁,加藤宣之

    第21回中国四国ウイルス研究会 

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    開催年月日: 2005年6月18日 - 2005年6月19日

    開催地:岡山県倉敷市  

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  • C型肝炎ウイルス(HCV)レプリコン細胞および全長HCV RNA複製細胞を用いたcDNAマイクロアレイ解析

    阿部健一,池田正徳,*團迫浩方,仲 一仁,下遠野邦忠,加藤宣之

    第52回日本ウイルス学会学術集会・総会 

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    開催年月日: 2004年11月21日 - 2004年11月23日

    開催地:横浜市  

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  • HCV-O(1B-2)株由来の全長HCV RNA複製系の開発

    池田正徳,阿部健一,*團迫浩方,中村孝志,仲 一仁,加藤宣之

    第52回日本ウイルス学会学術集会・総会 

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    開催年月日: 2004年11月21日 - 2004年11月23日

    開催地:横浜市  

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  • C型肝炎ウイルスNS5B蛋白質によるTLR3シグナル経路の活性化

    仲 一仁,*團迫浩方,小林直哉,池田正徳,加藤宣之

    第52回日本ウイルス学会学術集会・総会 

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    開催年月日: 2004年11月21日 - 2004年11月23日

    開催地:横浜市  

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  • Distraction of interferon signaling pathway in non-cancerous hepatocytes by HCV proteins.

    *Hiromichi Dansako, Kazuhito Naka, Naoya Kobayashi, Masanori Ikeda and Nobuyuki Kato

    11th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2004年10月3日 - 2004年10月7日

    開催地:Heidelberg, Germany  

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  • Hepatitis C virus NS5B avtivates TLR3 signaling pathway in non-cancerous hepatocytes.

    Kazuhito Naka, *Hiromichi Dansako, Naoya Kobayashi, Masanori Ikeda and Nobuyuki Kato

    11th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2004年10月3日 - 2004年10月7日

    開催地:Heidelberg, Germany  

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  • cDNA microarray analysis to compare HCV subgenomic and genome-length RNA replicating cells with their cured cells.

    Ken-ichi Abe, Masanori Ikeda, *Hiromichi Dansako, Kazuhito Naka, Kunitada Shimotohno and Nobuyuki Kato

    11th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2004年10月3日 - 2004年10月7日

    開催地:Heidelberg, Germany  

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  • Characterization of cured cells derived from a clonal Huh-7 cell line replicating a newly established genome-length HCV RNA(HCV-O).

    Masanori Ikeda, Ken-ichi Abe, *Hiromichi Dansako, Takashi Nakamura, Kazuhito Naka and Nobuyuki Kato

    11th International Symposium on Hepatitis C Virus and Related Viruses 

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    開催年月日: 2004年10月3日 - 2004年10月7日

    開催地:Heidelberg, Germany  

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  • C型肝炎ウイルスレプリコン細胞を用いたcDNAマイクロアレイ解析

    阿部 健一,池田 正徳,*團迫浩方,仲 一仁,下遠野 邦忠,加藤宣之

    第20回中国四国ウイルス研究会 

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    開催年月日: 2004年6月26日 - 2004年6月27日

    開催地:高知市  

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  • C型肝炎ウイルス蛋白質によるインターフェロンシグナル伝達経路の活性化

    *團迫浩方,仲 一仁,池田 正徳,加藤宣之

    第20回中国四国ウイルス研究会 

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    開催年月日: 2004年6月26日 - 2004年6月27日

    開催地:高知市  

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  • Establishment of a hepatitis C virus subgenomic replicon derived from human hepatocytes infected in vitro.

    Nobuyuki Kato, Kazuo Sugiyama, Katsuyuki Namba, *Hiromichi Dansako, Takashi Nakamura, Kazuhito Naka, Akito Nozaki snd Kunitada Shimotohno

    10 th International Meeting of Hepatitis C Virus and Related Viruses 

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    開催年月日: 2003年12月2日 - 2003年12月6日

    開催地:Kyoto, Japan  

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  • Differential activation of interferon-inducible genes by hepatitis C virus core protein mediated by the interferon stimulated response element.

    *Hiromichi Dansako, Atsushi Naganuma, Takashi Nakamura, Akito Nozaki and Nobuyuki Kato

    10 th International Meeting of Hepatitis C Virus and Related Viruses 

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    開催年月日: 2003年12月2日 - 2003年12月6日

    開催地:Kyoto, Japan  

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  • Establishment of interferon-resistant hepatitis C virus subgenomic replicons.

    Kazuhito Naka, Katsuyuki Namba, Takashi Nakamura, *Hiromichi Dansako, Akito Nozaki, Kunitada Shimotohno and Nobuyuki Kato

    10 th International Meeting of Hepatitis C Virus and Related Viruses 

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    開催年月日: 2003年12月2日 - 2003年12月6日

    開催地:Kyoto, Japan  

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  • Genetic evolution of hepatitis C virus subgenomic replicon in long-term culture.

    Nobuyuki Kato, Takashi Nakamura, *Hiromichi Dansako, Katsuyuki Namba, Takahiko Tamura, Akito Nozaki, Kazuhito Naka and Kunitada Shimotohno

    10 th International Meeting of Hepatitis C Virus and Related Viruses 

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    開催年月日: 2003年12月2日 - 2003年12月6日

    開催地:Kyoto, Japan  

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  • 長期培養におけるC型肝炎ウイルスsubgenomic repliconの遺伝的変異と多様性

    中村孝志,*團迫浩方,難波克行,田村隆彦,仲 一仁,野崎昭人,下遠野邦忠,加藤宣之

    第51回日本ウイルス学会学術集会・総会 

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    開催年月日: 2003年10月27日 - 2003年10月29日

    開催地:京都市  

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  • C型肝炎ウイルス(HCV)感染ヒト肝細胞由来の新規HCVsubgenomic replicon細胞の樹立

    加藤宣之,杉山和夫,難波克行,*團迫浩方,中村孝志,仲 一仁,野崎昭人,下遠野邦忠

    第51回日本ウイルス学会学術集会・総会 

     詳細を見る

    開催年月日: 2003年10月27日 - 2003年10月29日

    開催地:京都市  

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  • C型肝炎ウイルス蛋白質によるインターフェロンシグナル伝達系の活性化

    *團迫浩方,中村孝志,仲 一仁,野崎昭人,加藤宣之

    第51回日本ウイルス学会学術集会・総会 

     詳細を見る

    開催年月日: 2003年10月27日 - 2003年10月29日

    開催地:京都市  

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  • インターフェロン抵抗性C型肝炎ウイルスsubgenomic replicon細胞の樹立

    難波克行,仲 一仁,中村孝志,*團迫浩方,野崎昭人,白鳥康史,下遠野邦忠,加藤宣之

    第51回日本ウイルス学会学術集会・総会 

     詳細を見る

    開催年月日: 2003年10月27日 - 2003年10月29日

    開催地:京都市  

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  • ヒト培養細胞におけるC型肝炎ウイルスコア蛋白質のDNA修復能に及ぼす影響

    *團迫浩方, 仲 一仁,長沼 篤,野崎昭人,加藤宣之

    第62回日本癌学会総会 

     詳細を見る

    開催年月日: 2003年9月25日 - 2003年9月27日

    開催地:名古屋市  

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  • C型肝炎ウイルス感染ヒト肝細胞由来の新規HCVサブジェノミックレプリコン細胞の樹立

    加藤宣之,杉山和夫,*團迫浩方, 仲 一仁,野崎昭人,下遠野邦忠

    第62回日本癌学会総会 

     詳細を見る

    開催年月日: 2003年9月25日 - 2003年9月27日

    開催地:名古屋市  

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  • インターフェロン刺激応答配列を介したC型肝炎ウイルスコア蛋白質の転写活性化能

    *團迫浩方, 長沼 篤,中村孝志,高見まり香,野崎昭人,加藤宣之

    第25回日本分子生物学会年会 

     詳細を見る

    開催年月日: 2002年11月11日 - 2002年11月14日

    開催地:横浜市  

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  • C型肝炎ウイルスコア蛋白質のインターフェロン刺激応答配列に対する転写活性化能

    *團迫浩方, 長沼 篤,中村孝志,高見まり香,野崎昭人,加藤宣之

    第50回日本ウイルス学会学術集会・総会 

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    開催年月日: 2002年10月16日 - 2002年10月18日

    開催地:札幌市  

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  • C型肝炎ウイルスコア蛋白質のインターフェロンシグナル伝達経路の活性化

    *團迫浩方, 長沼 篤,野崎昭人,加藤宣之

    第61回日本癌学会総会 

     詳細を見る

    開催年月日: 2002年10月1日 - 2002年10月3日

    開催地:東京  

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  • C型肝炎ウイルスコア蛋白質のDNA修復系に及ぼす影響

    * 團迫浩方, 長沼 篤,中村孝志,野崎昭人,加藤宣之

    第18回中国四国ウイルス研究会 

     詳細を見る

    開催年月日: 2002年5月25日 - 2002年5月26日

    開催地:岡山市  

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  • C型肝炎ウイルスコア蛋白質によるインターフェロンシグナル伝達経路の活性化

    長沼 篤,*團迫浩方, 池田房雄,中村孝志,高木 均,森 昌朋,野崎昭人,加藤宣之

    第24回日本分子生物学会年会 

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    開催年月日: 2001年12月

    開催地:横浜市  

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  • C型肝炎ウイルスコア蛋白質のDNA修復系の及ぼす影響

    *團迫浩方, 長沼 篤,野崎昭人,中村孝志,高木 均,森 昌朋,加藤宣之

    第24回日本分子生物学会年会 

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    開催年月日: 2001年12月

    開催地:横浜市  

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  • Non-myeloablative stem cell transplant with fludarabine-based preparative regimen for advanced hematological malignancies.

    Kozo Masuda, Katsuji Shinagawa, Kazuma Ikeda, Kinuyo Kaneda, Takayuki Fujiwara, * Dansako, Kensuke Kojima, Fumihiko Ishimaru and Mine Harada

    30th Annual Meeting of the International Society for Experimental Hematology 

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    開催年月日: 2001年8月

    開催地:Tokyo, Japan  

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  • Non-myeloablative stem cell transplantation with fludarabine based preparatory regimen in advanced hematologic malignancies.

    Kozo Masuda, Katsuji Shinagawa, Kazuma Ikeda, Kinuyo Kaneda, Takayuki Fujiwara, *Hiromichi Dansako, Kensuke Kojima, Fumihiko Ishimaru and Mine Harada

    第63回日本血液学会総会-アジア血液セッション- 

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    開催年月日: 2001年4月

    開催地:名古屋市  

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  • 先天性第?、第?因子合併欠乏症の遺伝子解析

    *團迫浩方, 石丸文彦,高井 豊,中瀬浩一,瀬崎伸夫,中山博之,竹中克斗,品川克至,池田和眞,新谷憲治,原田実根

    第62回日本血液学会総会 

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    開催年月日: 2000年3月

    開催地:福岡市  

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受賞

  • 生物学研究奨励賞

    2021年10月   公益財団法人 両備檉園記念財団  

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  • 岡山医学会賞・がん研究奨励賞(林原賞)

    2016年6月   岡山医学会  

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  • 学術奨励賞

    2016年5月   公益財団法人山陽放送学術文化財団  

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共同研究・競争的資金等の研究

  • 新規細胞株を用いたHBV宿主/制限因子の同定

    2021年

    国立研究開発法人 日本医療研究開発機構  肝炎等克服実用化研究事業(分担)  B型肝炎創薬実用化等研究事業

    團迫 浩方

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    担当区分:研究分担者 

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  • 不死化ヒト肝細胞株を用いた新規抗HCV療法の機序解析

    2021年

    国立研究開発法人 日本医療研究開発機構  肝炎等克服実用化研究事業(分担)  肝炎等克服緊急対策研究事業(分担)

    團迫 浩方

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    担当区分:研究分担者 

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  • B型肝炎ウイルス感染に伴う細胞老化機構の分子生物学的解析

    2021年

    公益財団法人 両備檉園記念財団  両備檉園記念財団研究助成 

    團迫 浩方

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    担当区分:研究代表者 

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  • B型肝炎ウイルス感染により細胞外に放出されるDAMPsの同定

    2019年

    公益財団法人 岡山医学振興会  岡山医学振興会研究助成  研究助成

    團迫 浩方

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    担当区分:研究代表者 

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  • HBVの感染増殖におけるエクソソームの役割

    2017年 - 2021年

    国立研究開発法人 日本医療研究開発機構  肝炎等克服実用化研究事業(分担)  B型肝炎創薬実用化等研究事業

    團迫 浩方

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    担当区分:研究分担者 

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  • 肝炎ウイルスの長期複製による肝がん誘発機構に関する研究

    研究課題/領域番号:16H05196  2016年04月 - 2019年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    加藤 宣之, 金 惠淑, 佐藤 伸哉, 團迫 浩方, 上田 優輝, 瀬島 寛恵, 谷 煒琳, 小野村 大地, 平本 洸貴

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    担当区分:研究分担者 

    配分額:17420000円 ( 直接経費:13400000円 、 間接経費:4020000円 )

    HBVやHCVの長期複製と発癌との関係を明らかにすることを目的として、以下に示す研究成果を得た。(1) HCV の長期複製により顕著に発現低下したCPB2遺伝子の発現制御にVCX2とAGR2が関わっていた。(2) ヒト不死化肝細胞株NKNT-3とヒト肝癌細胞株Li23由来でHBVに高感受性を示すサブクローン化細胞株の樹立に成功した。(3) HBV感染前後で有意な発現変動を示す数種類の遺伝子を同定した。(4) 培養細胞から産生されるexosomeを精製する方法並びにその定量法を開発した。HBV低感受性細胞から産生されるexosome量が、高感受性細胞由来の量より有意に高いことを明らかにした。

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  • 全長HCV RNA複製肝がん細胞株由来のエクソソーム内に存在するナチュラルキラー細胞を制御する機能性分子の同定

    2016年

    ギリアド・サイエンシズ株式会社  ギリアド・サイエンシズ株式会社研究助成  研究助成

    團迫 浩方

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    担当区分:研究代表者 

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  • B型肝炎ウイルスを認識する宿主因子cGASを特異的に亢進する薬剤の探索

    2016年

    公益財団法人 山陽放送学術文化財団  山陽放送学術文化財団研究助成  研究助成

    團迫 浩方

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    担当区分:研究代表者 

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  • ナチュラルキラー細胞による肝炎ウイルス感染認識機構の解明

    研究課題/領域番号:15K08498  2015年04月 - 2018年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    團迫 浩方

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    担当区分:研究代表者 

    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    本研究において、全てのHCV蛋白質を発現するヒト不死化肝PH5CH8細胞やHCV感染ヒト肝がんRSc細胞において、NKG2DリガンドであるULBP1の細胞表面発現が有為に亢進していることを明らかにした。NK細胞株NK-92細胞とHCV感染RSc細胞の共培養は細胞障害活性とインターフェロン(IFN)-γの産生を誘導し、HCV複製を抑制した。NK-92細胞はHCV感染RSc細胞から放出されたウイルス由来dsRNAの刺激により、IFN-γを産生誘導しているものと考えられる。これらの結果から、ULBP1はHCV感染肝細胞において、NK細胞が誘導する自然免疫応答の標的分子であることが示唆された。

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  • B型肝炎ウイルス(HBV)の感染増殖を制御する分子機構の解明

    2015年

    公益財団法人 ウエスコ学術振興財団  ウエスコ学術振興財団研究助成  研究助成

    團迫 浩方

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    担当区分:研究代表者 

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  • B型肝炎ウイルスによるインターフェロン-a抵抗性機構の解明

    2014年

    公益財団法人 両備檉園記念財団  両備檉園記念財団研究助成  研究助成

    團迫 浩方

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    担当区分:研究代表者 

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  • HCV感染に起因する肝病態の進展に係わる宿主因子に関する研究

    研究課題/領域番号:25293110  2013年04月 - 2016年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    加藤 宣之, 池田 正徳, 團迫 浩方, 佐藤 伸哉

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    担当区分:研究分担者 

    配分額:17030000円 ( 直接経費:13100000円 、 間接経費:3930000円 )

    HCV RNAの長期複製と発癌との関係を明らかにすることを目的として研究を行い、以下に示す成果を得た。(1) HCV RNAの長期複製により顕著に発現低下したCPB2とBASP1遺伝子について、発現低下の分子機序を解析し、その一端を解明した。(2) HCV RNAの長期複製により発現低下するmiR-22とmiR-34aを見出した。(3) ヒト肝細胞由来のExosomeを再現性良く安定的に調製できる方法を開発し、HCV RNA複製細胞の長期培養におけるExosomeの変動解析に応用した。(4) 不死化ヒト肝細胞を用いて新規HCV RNA複製細胞モデルの開発を試み、今後の研究に有用な知見を得た。

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  • エクソソームを介したC型肝炎ウイルス感染・非感染細胞間自然免疫応答シグナル伝達機構の解明

    2013年

    公益財団法人 岡山医学振興会  岡山医学振興会研究助成  研究助成

    團迫 浩方

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    担当区分:研究代表者 

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  • 新発想に基づく1b遺伝子型HCVの感染増殖システムの開発

    研究課題/領域番号:24659207  2012年

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究  挑戦的萌芽研究

    加藤 宣之, 團迫 浩方, 森 京子

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    担当区分:研究分担者 

    配分額:3770000円 ( 直接経費:2900000円 、 間接経費:870000円 )

    培養細胞を用いて遺伝子型1bのC型肝炎ウイルス(HCV)の感染増殖システムの開発を試みた。本研究では、2009年にHCV RNAの複製を許容する細胞株として見出したヒト肝癌細胞株Li23と世界中で汎用されているヒト肝癌細胞株HuH-7を用いてHCV陽性血清(1b遺伝子型)をこれら細胞株に添加してHCVを感染させた。種々な条件下で感染実験を行ったが、HCVの増殖を確認するには至らなかった。その原因の1つとしてHCV受容体の1つであるCLDN1の発現量が非常に低くなっていることを見出し、CLDN1の発現補充が必要であることが分かった。

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  • C型肝炎ウイルスに関する研究

    2009年

    公益財団法人 上原記念生命科学財団  海外留学助成リサーチフェローシップ  海外留学助成リサーチフェローシップ

    團迫 浩方

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    担当区分:研究代表者 

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  • HCVによる自然免疫攪乱機構の解明

    研究課題/領域番号:19790340  2007年 - 2008年

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    團迫 浩方

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    配分額:3650000円 ( 直接経費:3200000円 、 間接経費:450000円 )

    C型肝炎ウイルス(HCV)による自然免疫システムの撹乱機構の解明を目的として行った研究において、以下のような成果を得た。(1)従来の報告とは異なり、NS3-4A蛋白質はTRIF蛋白質を切断しておらず、自然免疫機構の抑制はRIG-I/IPS-1経路に限定されていた。(2)NS5B蛋白質によるIFN-βの産生はTLR3経路およびRIG-I/MDA5経路の活性化、さらには両経路の下流の転写因子IRF-3の活性化を経て誘導されていた。(3)NS5B蛋白質によるIFN-βの産生誘導はTRAF3やTRAF6のノックダウンにより亢進することを示した。また、活性化されたIRF-3の調節にTRAF6が関与している可能性が示唆された。(4)PH5CH8細胞において、NS5Bは二本鎖RNAを産生していることを示した。これらの研究成果により、HCVはこれら分子との相互作用により自然免疫システムを撹乱している可能性が示唆された。

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  • C型肝炎ウイルス治療薬の新規スクリーニングシステムの構築

    研究課題/領域番号:17790308  2005年 - 2006年

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    團迫 浩方

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    配分額:3400000円 ( 直接経費:3400000円 )

    C型慢性肝炎患者に対する治癒率の改善のためには、現在のインターフェロン(IFN)とリバビリンの併用療法の改善だけでなく、IFNよりもC型肝炎ウイルス(HCV)の排除に効果的な薬剤をスクリーニングすることも重要である。そこで、従来のシステム(レポーター蛋白質の酵素活性を利用し、細胞内のHCV RNA複製レベルを定量、しかし生細胞のままの定量は困難)より簡便かつ安価に大規模な薬剤スクリーニングを遂行するために、緑色蛍光蛋白質であるEGFPをレポーター蛋白質に用いて、生細胞のままHCV RNA複製レベルの定量を可能にするシステムの開発を試みた。前年度までに、このシステムに必要なEGFP遺伝子を含む全長HCV RNA複製細胞を数クローン樹立することができ、細胞内でのHCV蛋白質およびEGFPの発現や、EGFPによる蛍光は観察できている。今年度は、この樹立した全長HCV RNA複製細胞を用いて、生細胞のままHCV RNA複製レベルを定量できるシステムの構築を行った。樹立できた数クローンのうち、OGN/C-5B/KE細胞(EGFP遺伝子をネオマイシン耐性遺伝子の前に、また適応変異としてNS3領域にK1609Eのアミノ酸置換を導入した全長HCV RNAが持続的に複製している細胞)のあるクローンが最も効率よく経時的に蛍光強度を上昇していることが確認できた。この細胞にIFN-αを処理し、その蛍光強度を生細胞のまま測定したところ、IFN-αの濃度依存的に減少していた。また、その値は、リアルタイムPCR法により定量したHCV RNA量と相関していた。また、ウエスタンブロット法により、EGFPやHCVコア蛋白質も減少していることが確認された。IFN-α以外に、HCVの排除に効果を示すことが報告されているIFN-β、IFN-γ、シクロスポリンAやフルバスタチンを同様に処理したところ、その蛍光強度とHCV RNA量の値は相関していた。また、IFN-αとシクロスポリンAあるいはIFN-αとフルバスタチンの併用処理は、それぞれの単剤処理に比べ、その蛍光強度は減少していた。これらの結果は、生細胞のままHCV RNAの複製レベルを定量することができるシステムを開発することができ、また、種々の薬剤処理も可能であることを示している(今研究実績は、現在、投稿準備中である)。

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担当授業科目

  • 腫瘍ウイルス学I(演習・実習) (2020年度) 特別  - その他

  • 腫瘍ウイルス学I(講義・演習) (2020年度) 特別  - その他

  • 腫瘍ウイルス学II(演習・実習) (2020年度) 特別  - その他

  • 腫瘍ウイルス学II(講義・演習) (2020年度) 特別  - その他