2011 Fiscal Year Final Research Report
The specific SM molecular species that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication
| Project/Area Number |
21390145
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | 財団法人東京都医学総合研究所 (2011)
Tokyo Metropolitan Organization for Medical Research (2009-2010) |
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Principal Investigator |
KOHARA Michinori 財団法人東京都医学総合研究所, ゲノム医科学研究分野, 副参事研究員 (10250218)
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| Co-Investigator(Kenkyū-buntansha) |
HIRATA Yuuichi 財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (50439452)
MUNAKATA Tsubasa 財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主席研究員 (50420237)
TOKUNAGA Yuuko 財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (80555011)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 細胞 |
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| Research Abstract |
Lipids are key components in the viral life cycle that affect host-pathogen interactions. In this study, we investigated the effect of HCV infection on sphingolipid metabolism, especially on endogenous SM levels, and the relationship between HCV replication and endogenous SM molecular species. We demonstrated that HCV induces the expression of the genes encoding sphingomyelin(SM) synthases. We observed associated increases of both total and individual sphingolipid molecular species, as assessed in human hepatocytes and in the detergent-resistant membrane(DRM) fraction in which HCV replicates. SGMS-1 expression had a strong correlation with HCV replication. Inhibition of sphingolipid biosynthesis with a hepatotropic serine palmitoyltransferase inhibitor, NA808, suppressed HCV-RNA production while also interfering with sphingolipid metabolism. Further, we identified the specific SM molecular species that comprise the DRM fraction and demonstrated that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication. Our results reveal that HCV alters sphingolipid metabolism to promote viral replication, providing new insights into the formation of the HCV replication complex and the involvement of host lipids in the HCV life cycle.
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[Journal Article] An orally available, small-molecule interferon inhibits hepatitis C virus replication2012
Author(s)
Konoishi H., Okamoto K., Ohmori Y., Yoshino H., Ohmori H., Ashiara M., Hirata Y., Ohta A., Sakamoto H., Hada N., Katsume A., Kohara M., MOrikawa K., Tsukuda T., Shimma N., Foster G., Alazawi W., Aoki Y., Arisawa M., Sudoh M.
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Journal Title
Sci. Comm
Volume: (in press)
Peer Reviewed
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[Journal Article] Monoclonal antibody 2-152a suppresses hepatitis C virus infection thorough betaine/GABA transporter-12011
Author(s)
Satoh M., Saito M., Takano T., Kasama Y., Nishimura T., Nishito Y., Hirata Y., Arai M., Sudoh M., Kai C., Kohara M., Tsukiyama-Kohara K.
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Journal Title
J. Infectious Disease
Volume: 204(8)
Pages: 1172-1180
Peer Reviewed
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[Journal Article] Augmentation of DHCR24 expression by hepatitis C virus infection facilitates viral replication in hepatocytes2011
Author(s)
Takano T., Tsukiyama-Kohara K., Hayashi M., Hirata Y., Satoh M., Tateno C., Hayashi Y., Hishima T., Funata N., Sudo M., Kohara M.
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Journal Title
J. Hepatology
Volume: 55
Pages: 512-521
Peer Reviewed
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[Journal Article] Evaluation of a recombinant measles virus expressing hepatitis C virus envelope proteins by infection of human PBL-NOD/Scid/Jak3null mouse2010
Author(s)
Satoh M., Saito M., Tanaka K., Iwanaga S., Salem N E., Seki T., Okada S., Kohara M., Harada S., Kai C., Tsukiyama-Kohara K.
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Journal Title
Comp Immunol Microbiol Infect Dis
Volume: 33(6)
Pages: 81-88
Peer Reviewed
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[Journal Article] Pathogenesis of hepatitis C virus infection in Tupaia belangeri2010
Author(s)
Amako Y., Tsukiyama-Kohara K., Katsume A., Hirata Y., Sekiguchi S., Tobita Y., Hayashi Y., Hishima T., Funata N., Yonekawa H., Kohara M.
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Journal Title
J. Virology
Volume: 84(1)
Pages: 303-311
Peer Reviewed
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[Journal Article] Hepatitis C virus impairs P53 via persistent over-expression of 3β-hydroxysterolΔ24-reductase2009
Author(s)
Nishimura T., Kohara M., Izumi K., Kasama Y., Hirata Y., Huang Y., Shuda M., Nuriya H., Tokunaga Y., Sato M., Saito M., Kai C. and Tsukiyama-Kohara K.
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Journal Title
J. Biol. Chem
Volume: 284(52)
Pages: 36442-36452
Peer Reviewed
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[Journal Article] Increased rate of death related to presence of viremia among hepatitis C virus antibody-positive subjects in a community-based cohort study2009
Author(s)
Uto H., Stuver S. O., Hayashi K., Kumagai K., Sasaki F., Kanmura S., Numata M., Moriuchi A., Hasegawa S., Oketani M., Ido A., Kusumoto K., Hasuike S., Nagata K., Kohara M. and Tsubouchi H.
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Journal Title
Hepatology
Volume: 50(2)
Pages: 393-9
Peer Reviewed
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[Journal Article] Disruption of IFN signaling and HCV synergistically enhance lymphoproliferation through type II CD95 and interleukins2009
Author(s)
Machida K., Tsukiyama-Kohara K., Sekiguchi S., Seike E., Tone S., Hayashi Y., Kasama Y., Shimizu M., Takahashi H., Taya C., Yonekawa H., Tanaka N. and Kohara M.
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Journal Title
Gastroenterology
Volume: 137(1)
Pages: 285-296
Peer Reviewed
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