Analysis for molecular mechanism of hepatitis C virus(HCV)-induced protein associated with persistent HCV infection

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The mechanisms underlying the persistence of Hepatitis C virus(HCV) infection are hypothesized to involve viral proteins abrogating the host immune response. Here, we report that HCV NS3/4A protease is associated with production of the C4 fragment and that this action affects the host immune response. In vitro, HCV NS3/4A protease showed concentration-dependent cleavage of C4 and a HCV NS3/4A protease inhibitor inhibited this cleavage. Functionally, cleavage of C4by HCV NS3/4A protease inhibited the classical pathway and this inhibition was also abrogated by a HCV NS3/4A protease inhibitor. Our results indicate that HCV NS3/4A protease inhibits complement activation through cleavage of C4, and that C4 cleavage by HCV NS3/4A protease should be one of the mechanisms underlying persistent HCV infection.