2007 Fiscal Year Final Research Report Summary
24-dehydrocholesterol reductase(DHCR24) inhibitor suppresses HCV replication
| Project/Area Number |
18390146
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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 | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
KOHARA Michinori Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Organization for Medical Research,The Tokyo Metropolitan Institute of Medical Sci, Head (10250218)
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| Co-Investigator(Kenkyū-buntansha) |
TAKANO Takashi The Tokyo Metropolitan Institute of Medical Science., Tokyo Metropolitan Organization for Medical Research, Researcher (20462781)
HAYASHI Masahiro The Tokyo Metropolitan Institute of Medical Science., Tokyo Metropolitan Organization for Medical Research, Researcher (70446566)
YASUI Fumihiko The Tokyo Metropolitan Institute of Medical Science., Tokyo Metropolitan Organization for Medical Research, Researcher (40399473)
INOUE Kazuaki Showa University, 医学部, Assistant Professor (90232529)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Hepatitis C Virus / Replication / Lipid raft / HCV replicon / Host factor |
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| Research Abstract |
Hepatitis C virus (HCV) frequently causes chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). We previously established the conditional full-length HCV gene expressing HepG2 cells and observed their increased tumorigenicity after 44 days passage (RzM6 44 days cells). In order to clarify the existence of antigens whose expression level has been changed according to the tumorigenicity, we established the monoclonal antibodies (MoAbs) against these cells. Over one thousand monoclonal antibodies were established, and their reactivities to RzM6 44 days cells were characterized. Several clones with significantly different reactivity to these cells, we first characterized clone 2-152, and it recognized approximately 55 killodalton (kDa.) molecule (p55). Therefore, we identified p55 molecule by MALDI-TOF/MS as 24-dehydrocholesterol reductase (DHCR24).
DHCR24 is a enzyme in the cholesterol biosynthetic pathway. U18666A is an inhibitor of DHCR24 and suppresses replication of the hepatitis C virus (HCV) replicon cells. We investigated the anti-HCV effect of U18666A against intact HCV using chimeric mice with humanized liver infected with HCV genotype 1a or 1b. We administered U18666A into HCV infected chimeric mice and succeeded in reducing the HCV RNA levels in serum and liver to 1/10-1/100 of the levels prior to the 8 day treatment. Furthermore, combined treatment with pegylated interferon reduced the HCV RNA levels to less than 1/1000 of the control levels. We strongly suggest that suppression of DHCR24 reduces HCV replication, and therefore that the DHCR24 inhibitor is potentially a novel drug in the treatment of HCV infection.
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[Journal Article] SARS-CoV spike protein recombinant vaccinia virus efficiently induces neutralizing antibodies in spite of pre-immunization with vaccinia virus.2007
Author(s)
Masahiro Kitabatake, Shingo Inoue, Fumihiko Yasui, Shoji Yokochi, Masaaki Arai, Kouichi Morita, Hisatoshi Shida, Minoru Kidokoro, Fukashi Murai, Mai Quynh Le, Kouji Matsushima and Michinori Kohara.
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Journal Title
Vaccine 25
Pages: 630-637
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Production of infectious hepatitis C virus particles in three-dimensional cultures of the cell line carrying the genome-length dicistronic viral RNA of genotype 1b.2006
Author(s)
Kyoko Murakami, Koji Ishii, Yousuke Ishihara, Sayaka Yoshizaki, Keiko Tanaka, Yasufumi Gotoh, Hideki Aizaki, Michinori Kohara, Hiroshi Yoshioka, Yuichi Mori, Noboru Manabe, Ikuo Shoji, Tetsutaro Sata, Ralf Bartenschlager, Yoshiharu Matsuura, Tatsuo Miyamura and Tetsuro Suzuki.
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Journal Title
Virology 351
Pages: 381-392
Description
「研究成果報告書概要(欧文)」より
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