Study on infection and maturation mechanisms of hepatitis C virus and its host response.

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To examine the molecular mechanisms of hepatitis C virus (HCV) infection, we prepared pseudotype viruses bearing unmodified HCV envelope proteins based on vesicular stomatitis virus (HCVpv) in both 293T and CHO cells. HCVpv generated in 293T cells (HCVpv/293T) exhibited a high infectivity to Huh7 cells but not to HepG2 cells. The infection of HCVpv/293T to Huh7 cells was neutralized by anti-hCD81 antibody, as reported for the pseudotype viruses based on murine leukemia virus (HCVpp) generated in 293T cells. In contrast, HCVpv generated in CHO cells (HCVpv/CHO) exhibited a high infectivity to hCD81-negative HepG2 cells and a weak infectivity to Huh7 cells. These results indicate that HCVpv/293T and HCVpv/CHO exhibit hCD81-dependent and -independent infectivity, respectively. Sera taken from chronic hepatitis C patients efficiently neutralized HCVpv/293T infection, as reported for HCVpp infection, whereas only a slight inhibition of HCVpv/CHO infection was observed. Naturally occurring HCV particles in serum taken from a hepatitis C patient during the window period of infection also exhibited binding to both Huh7 and HepG2 cells. In conclusion, these results indicate that the cell tropism of the HCV pseudotype viruses is determined by the producing cell lines, and that at least two types of HCV particles bearing similar properties to the pseudotype viruses exhibiting hCD81-dependent and -independent infection circulate in the serum of hepatitis C patients.