[Mechanism of persistence in HCV infection].
One of the prominent features of hepatitis C virus (HCV) is persistent infection, which is assumed to be a crucial event as a result of evading host defense system. Type I interferon beta (IFN- beta) system is induced rapidly after viral infection and plays a central role in innate immunity. Upon immediate induction of type I IFN as host first defense line, interferon regulatory factor-3 (IRF-3) is phosphorylated, formed of homodimer and translocates to nucleus. IFN-beta induction due to new castle disease virus (NDV) was significantly decreasd after the expression of full HCV genome (HCR6-Rz). Similar modification was observed in cell line expressing core to the NS2 protein region (HCR6-Fse). However, this decreasing was not observed in cell line expressing NS2 to the NS5B region (HCR6-Age). IRF-3 dimer formation induced by NDV infection was also suppressed after the expression of HCR6-Rz and HCR6-Fse, but not HCR6-Age. We further analyzed using transiently expressed HCV core, E1 or E2 in HepG2 cells. The suppression of IRF-3 dimer formation was caused by HCV core protein alone. These results indicated that a new crucial biological function of HCV core protein that may be related to persistence and pathogenesis of HCV.
Kohara
Michinori
M
Microbiology of Cell Biology, Tokyo Metropolitan Institute of Medical Science, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo 113-8613 Japan. mkohara@rinshoken.or.jp
Inoue
Kazuaki
K
D021581:Active Transport, Cell Nucleus; D004268:DNA-Binding Proteins / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism; D014758:Viral Core Proteins
D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D014157:Transcription Factors; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D016899:Interferon-beta