| 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)
楳原 琢哉 (財)東京都医学研究機構, 東京都臨床医学総合研究所, 研究員 (00415548)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,830,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2007: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2006: ¥7,600,000 (Direct Cost: ¥7,600,000)
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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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