Updated on 2023/10/19

写真a

 
NAMBA Hikaru
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Assistant Professor
Position
Assistant Professor
External link

Degree

  • 博士(医学) ( 岡山大学 )

  • 修士(薬学) ( 岡山大学 )

Research Interests

  • Virology

  • ウイルス学

  • Sugar

  • Gene expression control

Research Areas

  • Life Science / Molecular biology

  • Life Science / Virology

  • Life Science / Applied molecular and cellular biology  / Effects of sugars on cellular functions

  • Life Science / Applied microbiology  / Viral vector

Professional Memberships

 

Papers

  • 日本での突発性発疹の罹患年齢の上昇と感染様式 Reviewed

    鳥越貞義, 渡辺正博, 難波ひかる, 山田雅夫

    日本小児科学雑誌   126 ( 3 )   494 - 499   2022.3

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  • Nectin-2 Acts as a Viral Entry Mediated Molecule That Binds to Human Herpesvirus 6B Glycoprotein B Reviewed

    Hirohito Ogawa, Daisuke Fujikura, Hikaru Namba, Nobuko Yamashita, Tomoyuki Honda, Masao Yamada

    Viruses   14 ( 1 )   160 - 160   2022.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    Human herpesvirus 6B (HHV-6B) is a T-lymphotropic virus and the etiological agent of exanthem subitum. HHV-6B is present in a latent or persistent form after primary infection and is produced in the salivary glands or transmitted to this organ. Infected individuals continue to secrete the virus in their saliva, which is thus considered a source for virus transmission. HHV-6B primarily propagates in T cells because its entry receptor, CD134, is mainly expressed by activated T cells. The virus then spreads to the host’s organs, including the salivary glands, nervous system, and liver. However, CD134 expression is not detected in these organs. Therefore, HHV-6B may be entering cells via a currently unidentified cell surface molecule, but the mechanisms for this have not yet been investigated. In this study, we investigated a CD134-independent virus entry mechanism in the parotid-derived cell line HSY. First, we confirmed viral infection in CD134-membrane unanchored HSY cells. We then determined that nectin cell adhesion molecule 2 (nectin-2) mediated virus entry and that HHV-6B-insensitive T-cells transduced with nectin-2 were transformed into virus-permissive cells. We also found that virus entry was significantly reduced in nectin-2 knockout parotid-derived cells. Furthermore, we showed that HHV-6B glycoprotein B (gB) interacted with the nectin-2 V-set domain. The results suggest that nectin-2 acts as an HHV-6B entry-mediated protein.

    DOI: 10.3390/v14010160

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  • Risk assessment for hepatitis E virus infection from domestic pigs introduced into an experimental animal facility in a medical school. Reviewed

    Hirohito Ogawa, Haruko Hirayama, Satsuki Tanaka, Norio Yata, Hikaru Namba, Nobuko Yamashita, Kenzo Yonemitsu, Ken Maeda, Katsumi Mominoki, Masao Yamada

    The Journal of veterinary medical science   81 ( 8 )   1191 - 1196   2019.8

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:JAPAN SOC VET SCI  

    Hepatitis E virus (HEV) is known to cause zoonotic infections from pigs, wild boars and deer. Domestic pigs have been used as an experimental animal model in medical research and training; however, the risks of HEV infection from pigs during animal experiments are largely unknown. Here, we retrospectively investigated the seroprevalence and detection rates of viral RNA in 73 domestic pigs (average 34.5 kg) introduced into an animal experimental facility in a medical school during 2012-2016. We detected anti-HEV immunoglobulin G antibodies in 24 of 73 plasma samples (32.9%), though none of the samples were positive for viral RNA. Plasma samples of 18 pigs were sequentially monitored and were classified into four patterns: sustained positive (5 pigs), sustained negative (5 pigs), conversion to positive (6 pigs) and conversion to negative (2 pigs). HEV genomes were detected in 2 of 4 liver samples from pigs that were transported from the same farm during 2016-2017. Two viral sequences of the overlapping open reading frame (ORF) 2/3 region (97 bp) were identical and phylogenetically fell into genotype 3. A 459-bp length of the ORF2 region of an amplified fragment from a pig transported in 2017 was clustered with the wbJYG1 isolate (subgenotype 3b) with 91.5% (420/459 bp) nucleotide identity. Based on our results, we suggest that domestic pigs introduced into animal facilities carry a potential risk of HEV infection to researchers, trainees and facility staff. Continuous surveillance and precautions are important to prevent HEV infection in animal facilities.

    DOI: 10.1292/jvms.19-0086

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  • 岡山大学自然生命科学研究支援センターに搬入される家畜ブタのE型肝炎ウイルス感染状況について

    小川 寛人, 平山 晴子, 田中 爽暉, 矢田 範夫, 難波 ひかる, 山下 信子, 米満 研三, 前田 健, 樅木 勝巳, 山田 雅夫

    岡山実験動物研究会報   ( 35 )   62 - 63   2019.6

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  • Metabolic pathway catalyzed by Vanin-1 pantetheinase plays a suppressive role in influenza virus replication in human alveolar epithelial A549 cells Reviewed International journal

    Nobuko Yamashita, Masato Yashiro, Hirohito Ogawa, Hikaru Namba, Nobuyuki Nosaka, Yousuke Fujii, Tsuneo Morishima, Hirokazu Tsukahara, Masao Yamada

    Biochemical and Biophysical Research Communications   489 ( 4 )   466 - 471   2017.8

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.bbrc.2017.05.172

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  • Monitoring of human herpesviruses-6 and -7 DNA in saliva samples during the acute and convalescent phases of exanthem subitum. Reviewed International journal

    Yuki Miyazaki, Hikaru Namba, Sadayoshi Torigoe, Masahiro Watanabe, Nobuko Yamashita, Hirohito Ogawa, Tsuneo Morishima, Masao Yamada

    Journal of medical virology   89 ( 4 )   696 - 702   2017.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL  

    The amounts of the DNAs of human herpesviruses-6 (HHV-6) and -7 (HHV-7) in saliva samples were monitored during the acute and convalescent phases of exanthem subitum (ES) to elucidate the kinetics of virus shedding after ES. A total of 247 saliva samples were collected from 17 children (5 males and 12 females: 8-31 months old at onset). The monitoring period ranged from 152 to 721 days after onset, and in 15 children it was longer than 1 year. Among the 17 cases, 16 were attributed to HHV-6B, while a single case was attributed to HHV-7. Detection rates and average amounts of HHV-6 DNA in saliva samples after ES attributed to HHV-6B were low in the acute phase, increased to the maximum in the convalescent phase at 3-7 months, and then decreased. In addition, to investigate the source of infection, saliva samples from the older siblings (age 3-9 years) and parents of ES patients and children with a history of ES were also examined. The detection rate of HHV-6 DNA in saliva samples from 3- to 9-year-old children was significantly higher than the rate in adult saliva samples. Taken together, these findings suggest that the saliva of children in the convalescent phase of ES might be a more likely source of HHV-6 infection than that of adults. J. Med. Virol. 89:696-702, 2017. © 2016 Wiley Periodicals, Inc.

    DOI: 10.1002/jmv.24690

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    Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jmv.24690

  • Enhancive effects of d-glucose and its analogs on expression of d-glucose-unrelated transgenes in mammalian cells Reviewed International journal

    Miyuki Kimura, Hikaru Namba, Manabu Okubo, Mai Ezumi, Nao Susumu, Masao Yamada, Yujiro Arao

    Journal of Bioscience and Bioengineering   112 ( 2 )   194 - 201   2011.8

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    DOI: 10.1016/j.jbiosc.2011.04.010

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  • Characterization and usefulness of a monoclonal antibody against human herpesvirus-7 DNA polymerase processivity factor Reviewed

    Hikaru Namba

    Okayama Igakkai Zasshi (Journal of Okayama Medical Association)   117 ( 3 )   219 - 224   2005

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Okayama Medical Association  

    DOI: 10.4044/joma1947.117.3_219

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  • Interaction of human herpesvirus 6 with human CD34 positive cells. Reviewed International journal

    Hiroki Isomura, Mariko Yoshida, Hikaru Namba, Masao Yamada

    Journal of medical virology   70 ( 3 )   444 - 50   2003.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-LISS  

    We reported previously that human herpesvirus 6 (HHV-6) suppresses hematopoietic colony formation of erythroid (BFU-E), granulocyte/macrophage (CFU-GM), and megakaryocyte (CFU-Meg) lineages in vitro. Here we describe the interaction between HHV-6 and human CD34+ cells, which are a major source of hematopoietic progenitor cells. CD34+ cells were immunomagnetically isolated from cord blood mononuclear cells using anti-CD34+ antibodies coated onto either Dynabeads trade mark or MACS beads. The CD34+ population selected with Dynabeads showed a broad range of fluorescence. The population selected with MACS beads showed a narrow range of fluorescence. After infection with HHV-6, two transcripts of the immediate early genes were detected with both cell populations. HHV-6 suppressed colony formation of BFU-E, CFU-GM, and CFU-Meg. HHV-6 suppressed cell growth after 3 to 7 days culture in the presence of thrombopoietin (TPO). More differentiated CD34+ cells were more susceptible to the effects of HHV-6. These data indicate that the targets for hematopoietic suppression by HHV-6 are the differentiated cells.

    DOI: 10.1002/jmv.10415

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  • Monitoring of human herpesvirus-6 and -7 genomes in saliva samples of healthy adults by competitive quantitative PCR Reviewed International journal

    Nobukiyo Fujiwara, Hikaru Namba, Reiko Ohuchi, Hiroki Isomura, Fumio Uno, Mariko Yoshida, Shiro Nii, Masao Yamada

    Journal of Medical Virology   61 ( 2 )   208 - 213   2000.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1002/(sici)1096-9071(200006)61:2<208::aid-jmv6>3.0.co;2-1

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  • Suppressive effects of human herpesvirus-6 on thrombopoietin-inducible megakaryocytic colony formation in vitro Reviewed International journal

    Hiroki Isomura, Mariko Yoshida, Megumi Oda, Yoshiki Seino, Reiko Ohuchi, Fumio Uno, Masao Yamada, Hikaru Namba, Nobukiyo Fujiwara

    Journal of General Virology   81 ( 3 )   663 - 673   2000.3

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Microbiology Society  

    DOI: 10.1099/0022-1317-81-3-663

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  • Development of a dot blot neutralizing assay for HHV-6 and HHV-7 using specific monoclonal antibodies Reviewed International journal

    Takashi Tsukazaki, Mariko Yoshida, Hikaru Namba, Masao Yamada, Noshinobu Shimizu, Shiro Nii

    Journal of Virological Methods   73 ( 2 )   141 - 149   1998.8

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    DOI: 10.1016/s0166-0934(98)00051-2

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  • High-resolution immuno-scanning electron microscopy using a non-coating method: study of herpes simplex virus glycoproteins on the surface of virus particles and infected cells Reviewed International journal

    J. A. Padilla, F. Uno, M. Yamada, H. Namba, S. Nii

    Journal of Electron Microscopy   46 ( 2 )   171 - 180   1997.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Oxford University Press (OUP)  

    DOI: 10.1093/oxfordjournals.jmicro.a023505

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  • BDNF Gene Can Be Activated by Ca2+Signals without Involvement ofde NovoAP-1 Synthesis Reviewed International journal

    Kuniaki Sano, Hikaru Nanba, Akiko Tabuchi, Tomofusa Tsuchiya, Masaaki Tsuda

    Biochemical and Biophysical Research Communications   229 ( 3 )   788 - 793   1996.12

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    DOI: 10.1006/bbrc.1996.1881

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MISC

  • High-resolution immuno-scanning electron microscopy using a non-coating method: study of herpes simplex virus glycoproteins on the surface of virus particles and infected cells. Reviewed International journal

    J A Padilla, F Uno, M Yamada, H Namba, S Nii

    Journal of electron microscopy   46 ( 2 )   171 - 80   1997

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    Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:OXFORD UNIV PRESS  

    The expression of two glycoproteins, i.e. glycoprotein C (gC) and glycoprotein D (gD), of herpes simplex virus type 1 (HSV-1) on the surface of extracellular particles of this virus was examined by immuno-scanning electron microscopy. Scanning electron microscopy specimens of infected cells immuno-labelled against the glycoproteins with colloidal gold particles were prepared by a conventional coating and a non-coating method. Surface ultrastructure of infected cells and gold particles were observed more clearly with specimens prepared by the non-coating method. The appearance of virus particles in association with glycoprotein expression on these particles and on the surface of infected cells was then studied. Progeny virus particles began to appear 6 h after infection, increased in number as the infection proceeded, and covered most of the cell surface by 16 h. Six to 24 h after the infection, the labelling density for each glycoprotein on virus particles remained constant. The labelling density for gD was always higher than that for gC. The patch-like distribution of gold-labelling against gD was often detected on infected cell monolayers at the exponential and late stage of one cycle of virus growth. The labelling density for gD on virus particles was the highest on these produced in Vero and L-929 cells, moderate in MRC-5, BHK-21 and FL cells, and the lowest in HEp-2 cells.

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  • BDNF gene can Be activated by Ca2+ signals without involvement of de novo AP-1 synthesis. International journal

    K Sano, H Nanba, A Tabuchi, T Tsuchiya, M Tsuda

    Biochemical and biophysical research communications   229 ( 3 )   788 - 93   1996.12

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    Although stimulation of N-methyl-D-aspartate receptors or voltage-dependent calcium channels induces both the activation of c-fos and brain-derived neurotrophic factor (BDNF) genes, it is not certain how the activation of these genes is related. Using primary cultures of rat hippocampal neurons, we found that exposing the cells to cycloheximide allowed subsequent activation of BDNF mRNA expression, although activation of AP-1 DNA-binding activity resulting from the c-fos induction was abolished. Super-induction of BDNF gene was also caused by cycloheximide. The estimated half-life of BDNF mRNA was approximately 2.5 hrs, which was almost identical to that of c-fos mRNA. These results indicate that nascent AP-1 is not required for the activation of BDNF gene, leading to the notion that the BDNF gene can be activated by Ca2+ signals as an immediate early gene.

    DOI: 10.1006/bbrc.1996.1881

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  • インフルエンザウイルスの細胞侵入に対するセシウム添加の影響(in vitro)

    山下 信子, 小川 寛人, 難波 ひかる, 山田 雅夫

    臨床とウイルス   48 ( 3 )   S91 - S91   2020.9

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    Language:Japanese   Publishing type:Research paper, summary (national, other academic conference)   Publisher:日本臨床ウイルス学会  

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  • 唾液からのHHV6とHHV7のDNA検出率の前方視的検討 保育園入園半年と非就園半年の比較

    鳥越 貞義, 渡辺 正博, 難波 ひかる, 山下 信子, 小川 寛人, 山田 雅夫, 菅 秀, 根来 麻奈美

    臨床とウイルス   47 ( 2 )   S84 - S84   2019.4

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  • 岡山大学自然生命科学研究支援センターに搬入される家畜ブタのE型肝炎ウイルス感染状況について

    小川寛人, 平山晴子, 田中爽暉, 矢田範夫, 難波ひかる, 山下信子, 米満研三, 前田健, 樅木勝巳, 山田雅夫

    岡山実験動物研究会報   ( 35 )   2019

  • ヒトヘルペスウイルス6Bのテグメント蛋白質間の相互作用解析

    難波ひかる

    日本分子生物学会年会プログラム・要旨集(Web)   42nd   2019

  • HHV6Bテグメント蛋白質間相互作用の網羅的解析

    難波ひかる, 小川寛人, 山下信子, 山田雅夫

    日本ウイルス学会学術集会プログラム・予稿集(Web)   67th   2019

  • セシウムがインフルエンザウイルス増殖に及ぼす影響

    山下信子, 小川寛人, 難波ひかる, 山田雅夫

    日本ウイルス学会学術集会プログラム・予稿集(Web)   67th   2019

  • 養豚農場から大学動物実験施設に搬入される家畜ブタのE型肝炎ウイルス感染状況について

    小川 寛人, 平山 晴子, 田中 爽暉, 矢田 範夫, 難波 ひかる, 山下 信子, 米満 研三, 前田 健, 樅木 勝巳, 山田 雅夫

    日本獣医学会学術集会講演要旨集   161回   475 - 475   2018.8

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  • 動物実験施設に搬入される家畜ブタにおけるE型肝炎ウイルスの遺伝子検出および血清学的解析

    小川 寛人, 難波 ひかる, 山下 信子, 山田 雅夫, 田中 爽暉, 矢田 範夫, 平山 晴子, 樅木 勝巳, 米満 研三, 前田 健

    臨床とウイルス   46 ( 2 )   S58 - S58   2018.4

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  • 抗GFP-Nanobody共免疫沈降法によるウイルステグメント蛋白質の相互作用解析

    難波 ひかる

    生命科学系学会合同年次大会   2017年度   [3LBA - 114]   2017.12

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  • Metabolic pathway catalyzed by Vanin-1 pantetheinase plays a suppressive role in influenza virus replication in human alveolar epithelial A549 cells. International journal

    Nobuko Yamashita, Masato Yashiro, Hirohito Ogawa, Hikaru Namba, Nobuyuki Nosaka, Yousuke Fujii, Tsuneo Morishima, Hirokazu Tsukahara, Masao Yamada

    Biochemical and biophysical research communications   489 ( 4 )   466 - 471   2017.8

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    Our previous analysis of gene expression profiles in the peripheral blood from patients with influenza A (H1N1) pdm09 pneumonia revealed elevated transcription levels of the vanin-1 (vascular non-inflammatory molecule 1, VNN1) gene, which encodes an epithelial ectoenzyme with pantetheinase activity involved in recycling coenzyme A. Here, to elucidate the role of VNN1 in influenza A virus (IAV) H1N1 infection, we investigated the change of VNN1 expression in the context of IAV infection and the effects of its related substances, i.e., its direct substrate pantetheine and its two metabolites pantothenic acid and cysteamine on the replication of IAV in the human alveolar epithelial carcinoma cell line A549. The messenger RNA expression of VNN1 in A549 cells was significantly increased (by 4.9-fold) after IAV infection under an elevated concentration of pantetheine. Moreover, VNN1 mRNA levels were elevated by > 100-fold in response to pro-inflammatory cytokines, especially TNF-α and IL-1β. Pantetheine significantly reduced the IAV replication and IAV Matrix 1 (M1) mRNA levels when it was administered prior to and during infection. In addition, cysteamine treatment during IAV infection significantly reduced the viral replication and IAV M1 mRNA levels, whereas pantothenic acid did not. These findings suggest that the metabolic pathway catalyzed by VNN1 pantetheinase plays a suppressive role in IAV infection in the respiratory tract, especially in severe conditions under hypercytokinemia.

    DOI: 10.1016/j.bbrc.2017.05.172

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  • 集団保育児における唾液中のHHV-6とHHV-7DNAの排泄

    難波ひかる, 渡辺正博, 鳥越貞義, 山下信子, 山田雅夫

    臨床とウイルス   45 ( 2 )   S76 - S76   2017

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  • 抗GFP-Nanobody共免疫沈降法によるウイルステグメント蛋白質の相互作用解析

    難波ひかる

    日本生化学会大会(Web)   90th   [3LBA - 114]   2017

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  • 突発性発疹の感染様式に関する研究

    鳥越貞義, 難波ひかる, 渡辺正博, 宮崎裕樹, 森島恒雄, 山田雅夫

    臨床とウイルス   43 ( 2 )   S111 - S111   2015

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  • Vanin-1がインフルエンザウイルス感染に果たす役割

    山下 信子, 難波 ひかる, 山田 雅夫, 森島 恒雄

    臨床とウイルス   41 ( 2 )   S97 - S97   2013.5

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  • インフルエンザウイルス増殖に対する酸化ストレス関連遺伝子Vanin-1の影響

    山下信子, 難波ひかる, 山田雅夫, 森島恒雄

    日本ウイルス学会学術集会プログラム・抄録集   61st   2013

  • Vanin-1がインフルエンザウイルス感染に果たす役割

    山下信子, 山下信子, 難波ひかる, 山田雅夫, 森島恒雄

    日本ウイルス学会学術集会プログラム・抄録集   60th   2012

  • HHV-6Bテグメント蛋白質の単独発現系による細胞内局在解析

    難波ひかる, 山下信子, 山田雅夫

    日本ウイルス学会学術集会プログラム・抄録集   60th   2012

  • Enhancive effects of D-glucose and its analogs on expression of d-glucose-unrelated transgenes in mammalian cells. Reviewed

    Miyuki Kimura, Hikaru Namba, Manabu Okubo, Mai Ezumi, Nao Susumu, Masao Yamada, Yujiro Arao

    Journal of bioscience and bioengineering   112 ( 2 )   194 - 201   2011.8

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    Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:SOC BIOSCIENCE BIOENGINEERING JAPAN  

    We studied the effects of d-glucose on transgene expression in mammalian cells by a reporter gene assay using CV-1 cells and a CMV promoter-controlled EGFP gene. Treatment of CV-1 cells with 5% D-glucose unchanged the number of fluorescent cells in fluorescence microscopic observation but significantly intensified fluorescence in the fluorometric assay. Furthermore, EGFP itself and mRNA became more abundant in Western blot and quantitative RT-PCR analyses of 5% D-glucose-treated cells, respectively. These results indicate that elevated D-glucose can activate transgene expression via transcriptional stimulation, at least in part. The same concentrations of L-glucose led to only negligible increases in transgene expression, indicating that D-glucose's effect is different from its osmotic effect. The D-glucose-induced augmentation of fluorescence was observed not only in the experiment using the CMV promoter-controlled EGFP gene but also in experiments using the SV40 and RSV promoter-controlled ones, suggesting that elevated D-glucose can enhance transgene expression regulated by various promoters commonly used in transgene expression. The assessment of D-glucose analogs for their enhancive effects on transgene expression revealed that 1,6-anhydro-D-glucose and β-methyl-D-glucoside had stronger effects than D-glucose. From this result, we can expect to find more effective carbohydrates to enhance transgene expression. The α- and β-M-D-glucosides, which are slightly different from each other in three-dimensional structure, exerted largely distinct stimulative effects on transgene expression, suggesting that fundamental rules determine the enhancive effects of saccharides and that the modification of the saccharide by applying such rules will enable us to develop more powerful substances for transgene expression.

    DOI: 10.1016/j.jbiosc.2011.04.010

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  • G型ボツリヌス毒素遺伝子をコードするプラスミドの解析

    阪口義彦, 林哲也, 林哲也, 山本由弥子, 難波ひかる, 中山恵介, 馬少博, ZHANG Kai, 幸田知子, 小崎俊司, 小熊惠二

    日本細菌学雑誌   65 ( 1 )   162 - 162   2010

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  • コレラ菌およびコレラ毒素Bサブユニットに対するニワトリ抗体(IgY)の有用性

    平井一行, 衛藤友美, 大野佑子, 田村臣哉, 山本由弥子, 難波ひかる, 阪口義彦, 横田憲治, 小熊惠二

    日本薬学会年会要旨集   130th ( 3 )   84 - 84   2010

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  • G型ボツリヌス毒素遺伝子をコードするプラスミドの解析

    阪口義彦, 林哲也, 林哲也, 中山恵介, 山本由弥子, 難波ひかる, 細見晃司, 幸田知子, 向本雅郁, 小崎俊司, 小熊惠二

    日本ゲノム微生物学会年会要旨集   4th   2010

  • 哺乳動物培養細胞における糖応答シグナルの解析

    難波ひかる, 荒尾雄二郎

    日本分子生物学会年会講演要旨集   32nd ( Vol.1 )   2009

  • C型とD型ボツリヌス菌ホスホリパーゼCの酵素活性と生物活性

    阪口義彦, 小田真隆, 山本由弥子, 難波ひかる, MA Shaobo, ZHANG Kai, 田村臣哉, 唐澤忠宏, 小林敬子, 永浜政博, 櫻井純, 小熊恵二

    日本分子生物学会年会講演要旨集   32nd ( Vol.2 )   2009

  • ウイルスプロモーターからの遺伝子発現に対する糖の増大効果

    大久保学, 難波ひかる, 木村美幸, 荒尾雄二郎

    日本ウイルス学会学術集会プログラム・抄録集   56th   2008

  • ヒトサイトメガロウイルス前初期遺伝子プロモーターで制御された遺伝子発現に対する糖の刺激効果

    大久保学, 難波ひかる, 木村美幸, 荒尾雄二郎

    日本ウイルス学会学術集会プログラム・抄録集   55th   2007

  • ウイルス由来プロモーターで制御された遺伝子発現に対する糖の刺激効果

    難波ひかる, 大久保学, 江角真依, 進七緒, 木村美幸, 荒尾雄二郎

    生化学   80回・30回   4T11 - 4   2007

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  • Characterization and usefulness of a monoclonal antibody against human herpesvirus-7 DNA polymerase processivity factor Reviewed

    難波ひかる

    岡山医学会雑誌   117 ( 3 )   219 - 224   2006

  • 単純ヘルペスウイルスの吸着・侵入による宿主細胞のエステラーゼ,並びに排出ポンプ活性の上昇

    ミラー真理, 大久保学, 難波ひかる, 木村美幸, 荒尾雄二郎

    日本ウイルス学会学術集会プログラム・抄録集   54th   2006

  • 落葉状天疱瘡に生じHHV-6の再活性化を認めなかったDDSによるdrug-induced hypersensitivity syndromeの1例

    濱田 利久, 秋山 尚範, 岩月 啓氏, 山田 潤, 藤本 亘, 吉田 まり子, 難波 ひかる, 山田 雅夫

    西日本皮膚科   65 ( 3 )   299 - 299   2003.6

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  • ICE症候群におけるヘルペスウイルスの関与

    永山 幹夫, 松尾 俊彦, 山口 樹一郎, 田村 直之, 楳田 知子, 大月 洋, 難波 ひかる

    緑内障   11 ( 臨増 )   131 - 131   2001.8

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  • Monitoring of human herpesvirus-6 and -7 genomes in saliva samples of healthy adults by competitive quantitative PCR Reviewed International journal

    Nobukiyo Fujiwara, Hikaru Namba, Reiko Ohuchi, Hiroki Isomura, Fumio Uno, Mariko Yoshida, Shiro Nii, Masao Yamada

    Journal of Medical Virology   61 ( 2 )   208 - 213   2000.6

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    Human herpesviruses-6 and -7 (HHV-6 and HHV-7) are thought to be transmitted during early infancy through saliva. However, the kinetics of the virus shedding in saliva of healthy adults, from whom children are assumed to acquire the viruses, is mostly unknown. This study was conducted to determine how many copies of the genome are secreted in saliva of healthy adults and to clarify the relationship between viral DNA load and virus isolation of HHV-6 and HHV-7. Competitive PCR was performed using primer sets in the U42 gene of each viral genome. In saliva samples from 29 healthy adults, HHV-6 and HHV-7 DNA was detected in 41.4% and 89.7%, respectively. The average copy number of the HHV-7 genome in the positive samples was higher than that of the HHV-6 genome. Follow-up studies of six seropositive individuals for 3 months showed that the amount of HHV-7 DNA was constant in each individual and that "high producers" and "low producers" could be distinguished. By contrast, the amount of HHV-6 DNA varied drastically over time in each individual. Although HHV-6 was never isolated from the saliva of any of the six individuals during the follow-up period, HHV-7 was isolated from each individual several times. The amount of HHV-7 DNA tended to be higher at the times when the virus was isolated than at the times when the virus was not isolated. These data demonstrate a striking contrast between HHV-6 and HHV-7 in the kinetics of genome and virus shedding.

    DOI: 10.1002/(sici)1096-9071(200006)61:2<208::aid-jmv6>3.0.co;2-1

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  • Suppressive effects of human herpesvirus-6 on thrombopoietin-inducible megakaryocytic colony formation in vitro. Reviewed International journal

    H Isomura, M Yoshida, H Namba, N Fujiwara, R Ohuchi, F Uno, M Oda, Y Seino, M Yamada

    The Journal of general virology   81 ( Pt 3 )   663 - 73   2000.3

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    Two clinical observations, the association of human herpesvirus-6 (HHV-6) with delayed engraftment after stem cell transplantation and thrombocytopenia concomitant with exanthema subitum, prompted us to evaluate the suppressive effects of HHV-6 on thrombopoiesis in vitro. Different culture conditions for thrombopoietin (TPO)-inducible colonies in semi-solid matrices were examined. Using cord blood mononuclear cells as the source of haematopoietic progenitors, two types of colonies, megakaryocyte colony-forming units (CFU-Meg) and non-CFU-Meg colonies, were established. The former colonies were identified by the presence of cells with translucent cytoplasm and highly refractile cell membrane, most of which were positive for the CD41 antigen. Although the plating efficiency of both types was much higher under serum-containing conditions than under serum-free conditions, the proportion of CFU-Meg to non-CFU-Meg colonies was consistently higher under serum-free conditions. The plating efficiency of CFU-Meg colonies was doubled by adding stem cell factor to the serum-free matrix. The effects of two variants of HHV-6 (HHV-6A and 6B) and human herpesvirus-7 (HHV-7) on TPO-inducible colonies were then compared. HHV-6B inhibited both CFU-Meg and non-CFU-Meg colony formation under serum-free and serum-containing conditions. HHV-6A had similar inhibitory effects. In contrast, HHV-7 had no effect on TPO-inducible colony formation. Heat-inactivation and ultra-filtration of the virus sample completely abolished the suppressive effect. After infection of CD34(+) cells with HHV-6, the viral genome was consistently detected by in situ hybridization. These data suggest that the direct effect of HHV-6 on haematopoietic progenitors is one of the major causes of the suppression of thrombopoiesis.

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  • Development of a dot blot neutralizing assay for HHV-6 and HHV-7 using specific monoclonal antibodies Reviewed International journal

    T Tsukazaki, M Yoshida, H Namba, M Yamada, N Shimizu, S Nii

    JOURNAL OF VIROLOGICAL METHODS   73 ( 2 )   141 - 149   1998.8

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    To elucidate further immune responses to human herpesviruses 6 and 7 (HHV-6 and -7), a neutralizing antibody assay was established for these viruses using a dot blot method. Three monoclonal antibodies against HHV-6 and 12 monoclonal antibodies against HHV-7 were developed and characterized by radio-immunoprecipitation. One monoclonal antibody which recognizes the 135 kDa late polypeptide of HHV-6 and several which recognize the 125 kDa late polypeptide of HHV-7 were selected to monitor virus growth by a dot blot antigen-detection method. The dot blot method was then used for the assay of HHV-6 and -7 neutralizing antibodies in human serum samples. The neutralization endpoints determined by the dot blot were comparable to those determined by immunofluorescence (IF). The neutralizing antibody titers appeared to correlate with the antibody titers determined by the indirect IF antibody test. The dot blot neutralization assay is easy to perform, is highly reproducible and objective when compared with the conventional methods based on cytopathology or IF for determining neutralization endpoints. (C) 1998 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0166-0934(98)00051-2

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  • High-resolution immuno-scanning electron microscopy using a non-coating method: study of herpes simplex virus glycoproteins on the surface of virus particles and infected cells Reviewed

    J. A. Padilla, F. Uno, M. Yamada, H. Namba, S. Nii

    Journal of Electron Microscopy   46 ( 2 )   171 - 180   1997.1

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    Language:English   Publisher:Oxford University Press (OUP)  

    The expression of two glycoproteins, i.e. glycoprotein C (gC) and glycoprotein D (gD). of herpes simplex virus type 1 (HSV-1) on the surface of extracellular particles of this virus was examined by immune-scanning electron microscopy. Scanning electron microscopy specimens of infected cells immuno-labelled against the glycoproteins with colloidal gold particles were prepared by a conventional coating and a non-coating method. Surface ultrastructure of infected cells and gold particles were observed more clearly with specimens prepared by the non-coating method. The appearance of virus particles in association with glycoprotein expression on these particles and on the surface of infected cells was then studied. Progeny virus particles began to appear 6 h after infection, increased in number as the infection proceeded, and covered most of the cell surface by 16 h. Six to 24 h after the infection, the labelling density for each glycoprotein on virus particles remained constant. The labelling density for gD was always higher than that for gc. The patch-like distribution of gold-labelling against go was often detected on infected cell monolayers al the exponential and late stage of one cycle of virus growth. The labelling density for go on virus particles was the highest on these produced in Vero and L-929 cells, moderate in MRC-5, BHK-21 and FL cells, and the lowest in HEp-2 cells.

    DOI: 10.1093/oxfordjournals.jmicro.a023505

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  • Long PCR and multiple SSCP for mutation analysis of a whole gene.

    難波ひかる, 花房裕子, 吉鷹知也, 松原長秀, 佃和憲, 谷野元彦, 清水憲二

    日本分子生物学会年会プログラム・講演要旨集   18th   1995

  • グルタミン酸応答で活性化される遺伝子発現カスケードの解析

    佐野訓明, 難波ひかる, 田岡章子, 市川大介, 田淵明子, 土屋友房, 津田正明

    日本薬学会年会要旨集   115th ( Pt 3 )   1995

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  • Possible regulation of BDNF mRNA expression by AP-1 binding activity induced via glutamate receptors.

    難波ひかる, 佐野訓明, 市川大介, 土屋友房, 津田正明

    日本分子生物学会年会プログラム・講演要旨集   17th   1994

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Presentations

  • Effect of cesium addition on influenza virus cell invasion

    2020.10.2 

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    Event date: 2020.10.2 - 2020.10.31

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:Niigata  

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  • Interaction analysis between tegument proteins of human herpesvirus 6B

    Hikaru Namba

    2019.12.4 

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    Event date: 2019.12.3 - 2019.12.6

    Language:Japanese  

    Venue:Fukuoka  

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  • Interaction analysis between tegument proteins of human herpesvirus 6B

    Hikaru Namba, Hiroto Ogawa, Nobuko Yamashita, Masao Yamada

    2019.10.30 

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    Event date: 2019.10.29 - 2019.10.31

    Language:Japanese   Presentation type:Poster presentation  

    Venue:Tokyo  

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  • A prospective study of DNA detection rates for HHV6 and HHV7 in infant saliva

    2019.5.25 

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    Event date: 2019.5.25 - 2019.5.26

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:Nagoya  

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  • Gene detection and serological analysis of hepatitis E virus in domestic pigs brought to animal testing facilities

    2018.9.11 

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    Event date: 2018.9.11 - 2018.9.13

    Language:Japanese   Presentation type:Poster presentation  

    Venue:Ibaraki  

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  • Interaction analysis of viral tegment proteins by anti-GFP-Nanobody co-immunoprecipitation

    Hikaru Namba

    2017.12.8 

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    Event date: 2017.12.6 - 2017.12.9

    Language:Japanese   Presentation type:Poster presentation  

    Venue:Kobe, Hyogo  

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  • Salivary Secretion of Three Betaherpesviruses in Nursery Schools

    2017 

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  • 集団保育児における唾液中のHHV-6とHHV-7 DNAの排泄

    第58回日本臨床ウイルス学会  2017 

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  • 集団保育児における唾液中の HHV-6 と HHV-7 DNA の排泄

    第32回中国四国ウイルス研究会  2017 

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  • 集団保育児における唾液中の3種ベータヘルペスウイルスDNAの排泄状況

    第65回日本ウイルス学会 学術集会  2017 

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  • Pantetheine- Vanin-1- Cysteamine 系は、A549 細胞でインフルエンザウイルス増殖を抑制する

    第31回中国四国ウイルス研究会  2016 

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  • ヒトヘルペスウイルス6B U65とU71蛋白質の 相互作用機構の解明

    第64回日本ウイルス学会 学術集会  2016 

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  • Pantetheine- Vanin-1- Cysteamine 系は、A549 細胞でインフルエンザウイルス増殖を抑制する

    第64回日本ウイルス学会 学術集会  2016 

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  • Analysis of Interaction between the U65 and U71 proteins of human herpesvirus 6B

    2016 

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  • 突発性発疹の感染様式に関する研究

    第56回 日本臨床ウイルス学会  2015 

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  • 突発性発疹患児急性期から回復期における唾液中のHHV-6B、HHV-7経時的モニタリング

    第63回日本ウイルス学会学術集会  2015 

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  • 突発性発疹患児における唾液中のHHV6、HHV7モニタリング

    第29回中国四国ウイルス研究会  2014 

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  • ヒトヘルペスウイルス6B U65とU71の共発現による局在変化

    第28回ヘルペスウイルス研究会  2013 

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  • Vanin-1がインフルエンザウイルス感染に果たす役割

    日本臨床ウイルス学会学術集会  2013 

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  • ヒトヘルペスウイルス6B U65とU71の共発現による局在変化

    第28回中国四国ウイルス研究会  2013 

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  • Vanin-1がインフルエンザウイルス感染に果たす役割

    日本ウイルス学会学術集会  2012 

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  • Vanin-1がインフルエンザウイルス感染に果たす役割

    第27回中国四国ウイルス研究会  2012 

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  • HHV-6Bテグメント蛋白質の単独発現系による細胞内局在解析

    日本ウイルス学会学術集会  2012 

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  • ヒトヘルペスウイルス6型テグメント蛋白質の局在解析

    第27回ヘルペスウイルス研究会  2012 

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  • ヒトヘルペスウイルス6型テグメント蛋白質の局在解析

    第27回中国四国ウイルス研究会  2012 

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  • G型ボツリヌス毒素遺伝子をコードするプラスミドの解析

    日本ゲノム微生物学会年会  2010 

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  • コレラ菌およびコレラ毒素Bサブユニットに対するニワトリ抗体(IgY)の有用性

    日本薬学会 第130年会(岡山)  2010 

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  • G型ボツリヌス毒素遺伝子をコードするプラスミドの解析

    第83回 日本細菌学会総会  2010 

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  • 哺乳動物培養細胞における糖応答シグナルの解析

    第32回日本分子生物学会年会  2009 

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  • 落葉状天疱瘡に生じHHV-6の再活性化をみとめなかったDDSによるDrug-induced Hypersensitivity Syndromeの1例

    日本皮膚科学会 第54回日本皮膚科学会西部支部学術大会  2002 

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  • ICE症候群におけるヘルペスウイルスの関与

    第12回日本緑内障学会  2001 

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Industrial property rights

  • Promoter activation method and protein production method using protein production medium

    HIKARU NAMBA, YUJIRO ARAO

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    Applicant:NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY

    Application no:特願2013-163530  Date applied:2013.8.6

    Announcement no:特開2013-240353  Date announced:2013.12.5

    Patent/Registration no:特許5748808  Date registered:2015.5.22  Date issued:2015.7.15

    Rights holder:NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY   Country of applicant:Domestic   Country of acquisition:Domestic

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  • CULTURE MEDIUM FOR PRODUCTION OF PROTEIN OR PROLIFERATION OF VIRUS

    HIKARU NAMBA, YUJIRO ARAO

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    Applicant:NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY

    Application no:特願2009-507454  Date applied:2008.3.17

    Patent/Registration no:特許第5634710号  Date registered:2014.10.24 

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  • CULTURE MEDIUM FOR PRODUCTION OF PROTEIN OR PROLIFERATION OF VIRUS

    HIKARU NAMBA, YUJIRO ARAO

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    Applicant:NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY

    Application no:特願2007-071390  Date applied:2007.3.17

    Announcement no:WO 2008/120570  Date announced:2008.10.9

    Publication no:WO2008-120570  Date published:2008109

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Research Projects

  • セシウムがインフルエンザウイルス・RSウイルス感染に及ぼす影響

    Grant number:20K08180  2020.04 - 2023.03

    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)

    山下 信子, 小川 寛人, 八代 将登, 難波 ひかる

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

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  • Investigation of host factors for severe influenza virus infection

    Grant number:26461585  2014.04 - 2017.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Yamashita Nobuko

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    Grant amount:\4940000 ( Direct expense: \3800000 、 Indirect expense:\1140000 )

    Results: (i) Increased expression of IL-11, Fas L, Angiotensin II receptor genes was observed in vascular endothelial cells, when influenza virus infected the respiratory epithelium (in vitro). It was thought to be an influenza virus specific response. (ii) VNN1 was newly identified as a gene involved in influenza virus replication in the respiratory epithelium. VNN1 is an enzyme that hydrolyzes pantetheine, and it was found that cysteamine which is a degradation product of pantetheine, has a virus replication inhibiting action.

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  • ウイルスプロモーターからの外来遺伝子発現に対する糖の促進効果に関する研究

    Grant number:20656138  2008 - 2009

    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

    荒尾 雄二郎, 難波 ひかる, 木村 美幸

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    Grant amount:\3400000 ( Direct expense: \3400000 )

    1 外来遺伝子発現に対する糖鎖の促進効果
    プルランを代表例として、CV-1細胞でのCMVプロモーター制御EGFP遺伝子の一過性発現に対する糖鎖の効果を調べると、濃度依存的に遺伝子発現を増加させ、12%で最大の効果を発揮した。プルラン以外の糖鎖である酵母マンナン、デキストラン、フルクトオリゴ糖、コンドロイチン硫酸でも有意な遺伝子発現増大効果が観察された。これらの知見は、本研究の応用性を広げるとともに、生物現象との共通性を示唆する点で重要である。
    2 ヘキソーストランスポーター(GLUT)が糖センサーであるか否かの検討
    GLUTを介して取込まれる蛍光グルコース類似体(2NBDG)を各種の糖の存在下でCV-1細胞に2時間取込ませ、2NBDG取込み量と各糖の外来遺伝子発現促進効果を比較したところ、糖濃度が100、500mMいずれの場合でも両者は相関しなかった。従って、GLUTは糖の遺伝子発現促進効果のセンサーではないと推定された。
    3 阻害剤等を用いた糖の促進機構の解析
    促進効果の高いラクチュロースと各種阻害剤を(1)の評価系で同時に作用させ、阻害剤の影響を検討した。ラクチュロースによる遺伝子発現増大は、G1阻害剤とG1/S阻害剤で低下し、G2/M阻害剤で相加的に増大した。従って、細胞周期、並びにそれ以外の因子の関与が推測され、その機構を解明する上で重要な手掛かりとなる。
    4 糖添加後早期における細胞内遺伝子発現状態の解析
    糖刺激早期(糖添加1時間後)におけるmRNAをマイクロアレイ法で解析した。その結果、RNAのスプライシング、結合、加工、代謝、並びにmRNAの代謝が活性化され、クロマチン、蛋白質-DNA複合体、及びヌクレオソームの集合状態が低下していると示唆された。添加後1時間以内にDNA構造体の乖離と転写の活性化が誘導されるというこの示唆は、その機構解明に大きな意義をもつ。

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  • Imunoresponse against Human herpesvirus-6 and Human herpesvirus-7

    Grant number:14570264  2002 - 2003

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    YOSHIDA Mariko, INAMBA Hikaru, YAMADA Masao

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    Grant amount:\3500000 ( Direct expense: \3500000 )

    Plasmacytoid dendritic cell (DC) precursors in human blood are now recognized as identical to natural alpha interferon (IFN-α)-producing cells (IPCs) and are thought to play an important role in antiviral immunity. Therefore, We tried to investigate the susceptibility as well as the cellular responses of DCs to two variants of human herpesvirus 6 (HHV-6), namely A and B, and human herpesvirus 7 (HHV-7). DCs are isolated from cord blood mononuclear ells (CBMCs) by magnetic-bead separation. Although HHV-6A, HHV-6B and HHV-7 are Closely related in DNA sequence, each has distinctive genomic, antigenic, and biological properties. First, DCs are infected with these viruses at various multiplicity of infection and examined by Facs for defection of surface antigen, by ELISA for production of cytokines, and by the transmission electron microscopy (TEM) for replication of the viruses. Based on the observation of TEM, all of these viruses infect DCs and produce progeny viruses. The reticular inclusion bodies with a skein-like appearance were commonly observed, which are the particular structure in the nuclei of infected cells with these viruses. In the expression of surface antigens, CD80, CD83, CD86, and HLA-DR, which are marker antigen for maturation of DCs, are determined on infected cells with HHV-6 more intensive than on HHV-7 infected cells. Both of HHV-6A and HHV-6B infections trigger DCs to produce vast amounts of IFN-α and induces DCs to differentiate into mature DCs. In contrast, DCs infected with HHV-7 do not produce IFN-α neither differentiate into mature DCs. Second, naive CD4^+ T cells obtained from CBMCs are co-cultured with virus-infected DCs and measured the CD4^+ T cells-induced cytokines. HHV-6B infected DCs stimulate naive CD4^+ T cells to produce IFN-γ and interleukin-10 (IL-10). HHV-6A or HHV-7 infected DCs stimulate naive CD4^+_T cells to produce IL-4, IL-5, IL-10, and IFN-γ. These findings suggest that producing large amount or IFN-α from infected DCs dose not contribute to a critical link between innate and adaptive immunity. Viral specific proteins may be an important role on the differentiation of DCs and on the following events to dictate T cell mediated immunity.

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  • Inhibitory Effects of Beta-herpesviruses on Hematopoiesis

    Grant number:13670299  2001 - 2002

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    YAMADA Masao, NAMBA Hikaru, ISOMURA Hiroki, YOSHIDA Mariko, ARAO Yujirou

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    Grant amount:\3600000 ( Direct expense: \3600000 )

    Human herpesvirus 6 (HHV-6), as well as human cytomegalovirus, is related to various severe complications after hematopoietic stem cell transplantation (SCT) under extensive use of immunosuppressive drugs. We monitored the activity of five herpesviruses including three beta-herpesviruses after allogeneic SCT, and showed that HHV-6 is associated with delayed engraftment of hematopoietic cells after SCT. In vitro models, however, have not proven the relationship between beta-herpesviruses and the clinical manifestations.
    We established the in vitro systems to assess the effects of HHV-6 and related beta herpesviruses on hematopoietic colony formation. We comparatively examined HHV-6A, HHV6B, and human herpesvirus 7 (HHV-7). We showed that both type of HHV-6 suppresses all three lineages of hematopoietic colony formation of erythroid (BFU-E), granulocyte /macrophage (CFU-GM), and megakaryocyte (CFU-Meg) in vitro. On the other hand, HHV-7 did not have any suppressive effect on in vitro hematopoietic colony formation..
    We focused on HHV-6B and further examined the interaction with human CD34+ cells, which are a major source of hematopoietic progenitor cells. CD34+ cells were immunomagnetically isolated from cord blood mononuclear cells using anti-CD34+ antibodies coated onto either Dynabeads or MACS beads. The CD34+ population selected with Dynabeads showed a broad range of fluorescence. The population selected with MACS beads showed a narrow range of fluorescence. After infection with HHV-6, Two transcripts of the immediate early genes were detected with both cell populations. HHV-6 suppressed colony formation of BFU-E, CFU-GM, and CFU-Meg. HHV-6 suppressed cell growth after 3 to 7 days culture in the presence of thrombopoietin (TPO). More differentiated CD34+ cells were more susceptible to the effects of HHV-6. These data indicate that the targets for hematopoietic suppression by HHV-6 are relatively differentiated cells that express a lower amount of the CD34 antigen (dim cells) among a heterogeneous cell population.

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  • Analysis of antigenic properties of human herpesvirus 7 and the host immune responses

    Grant number:10670285  1998 - 1999

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    YAMADA Masao, ISOMURA Hiroki, NAMBA Hikaru, YOSHIDA Mariko, OHUCHI Reiko

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    Grant amount:\2400000 ( Direct expense: \2400000 )

    To elucidate antigenic properties of human herpesviruses 6 and 7 (HHV-6 and -7), three monoclonal antibodies (Mabs) against HHV-6 and 13Mabs against HHV-7 were established and characterized by radio-immunoprecipitation. The 40-kDa phosphoprotein by recognized by a Mab (TK17) was the product of HHV-7 U27 gene. Among these Mabs, a Mab(IK3) which recognizes the 135-kDa late polypeptide of HHV-6 and several Mabs (TK3 and others) which recognize the 125-kDa late polypeptide of HHV-7 were selected to monitor virus growth by a dot blot antigen-detection method. Using the dot blot method, we established a neutralizing antibody assay for these viruses. The dot-blot neutralization assay is easy to perform, is highly reproducible and objective when compared with the conventional methods based on cytopathology or immunofluorescence for determining neutralization endpoints. Using this method, 55 sera from healthy adults were examined. In most individuals, neutralizing antibody titers against HHV-7 were much higher than those against HHV-6. Elevated neutralizing titers against HHV-7 might be attributed to continuous booster effects by persistent HHV-7 production in saliva. Furthermore, we monitored neutralizing antibody titers against these viruses in 15 children with documented history of exanthem subitum. Transferred antibody titers against these viruses from mothers were readily demonstrated by the neutralization test. Transferred antibody titers against HHV-7 were higher and remained longer after birth than those of HHV-6, and these findings were in accord with clinical observation that HHV-6 infection usually occurs earlier than HHV-7 infection. It is notable that no cross-reactive elevation of heterologous neutralizing antibody titer was observed.

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