Study on molecular mechanisms of hepatitis C virus infection.
| Project/Area Number |
16017252
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Osaka University |
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Principal Investigator |
MATSUURA Yoshiharu Osaka University, Research Institute for Microbial Diseases, Professor, 微生物研究所, 教授 (50157252)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2005: ¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 2004: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | HCV / Infection / Receptor / FGFR / 細胞融合 / リセプター |
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| Research Abstract |
Although several cell surface molecules such as hCD81, LDL-R, SR-B1, and DC-SIGN have been proposed as candidates for hepatitis C virus (HCV) receptor, it is still unclear if any of these molecules can play a role as a functional cellular receptor, due to the lack of robust and reliable in vitro cell culture systems to propagate HCV. As a surrogate system for the study of HCV infection, pseudotype viruses bearing HCV envelope glycoproteins based on vesicular stomatitis viruses (HCVpv) and retroviruses (HCVpp) have been developed. We have previously shown that human fibroblast growth factor receptor (hFGFR) 4 is a binding receptor for HCV based on the specific binding with HCVpv, HCV-like particles and authentic HCV particles in patient sera. Recently we found that HCVpv generated in 293T cells and CHO cells (HCVpv/CHO) exhibit hCD81-dependent and -independent infection, respectively. Infection of HCVpv/CHO to HepG2 cells was inhibited by hFGF2, a soluble protein representing the ectodomain of hFGFR5 fused with the Fe region of IgG (hFGFR5/Fc), or anti-hFGFR5 antibody. Overexpression of hFGFR5 in 293T and Huh7 cells enhanced the susceptibility to HCVpv/CHO infection. In contrast, siRNA-mediated knockdown of hFGFR5 in HepG2 cells resulted in the reduction of infectivity of HCVpv/CHO. Furthermore, binding of the authentic HCV particles in patient sera to HepG2 cells was inhibited by the hFGFR5/Fc. Finally, expression of hFGFR5 (but not hFGFR4) in CHO cells rendered them permissive for HCVpv/CHO infection. Together, these results suggest the possible involvement of hFGFR5 in the internalization process of HCV in a hCD81-independent fashion.
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Report
(3 results)
Research Products
(29 results)
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[Journal Article] Human VAP-B Is Involved in Hepatitis C Virus Replication through Interaction with NS5A and NS5B.2005
Author(s)
Hamamoto L, Nishimura Y., Okamoto T., Aizald H., Liu M., Mori Y., Abe T., Suzuki T., Lai M.M., Miyamura T., Moriishi K., Matsuura Y.
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Journal Title
J. Yirol. 79
Pages: 13473-13482
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Nuclear localization of Japanese encephalitis virus core protein enhances viral replication.2005
Author(s)
Mori Y., Okabayashi T., Yamashita T., Zhao Z., Wakita T., Yasui K, Hasebe F., Tadano M., Konishi E., Moriishi K, Matsuura Y.
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Journal Title
J. Virol. 79
Pages: 3448-3458
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Molecular determinants for subcellular localization of hepatitis C virus core protein.2005
Author(s)
Suzuki R., Sakamoto S., Tsutsumi T., Rikimaru-A., Tanaka K, Shimoike T., Moriishi K, Iwasaki T., Mizumoto K, Matsuura Y., Miyamura T., Suzuki T.
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Journal Title
1. Virol. 79
Pages: 1271-1281
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Pseudotype hepatitis C virus enters immature myeloid dendritic cells through the interaction with lectin.2004
Author(s)
Kaimori A., Kanto T., Limn C-K, Komoda Y., Old C., Inoue M., Miyatake H., hose I., Sakaldbara M., Yakushiji T., Takehara T., Matsuura Y., Hayashi N.
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Journal Title
Virology 324
Pages: 74-83
Description
「研究成果報告書概要(欧文)」より
Related Report
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