A structurally flexible and antigenically variable N-terminal domain of the hepatitis C virus E2/NS1 protein: implication for an escape from antibody

Abstract

Hepatitis C virus persists in most infected hosts, and causes chronic hepatitis, liver cirrhosis, and/or hepatocellular carcinoma in humans. During the infection the RNA genome of hepatitis C virus undergoes frequent missense mutations at one or two "hypervariable" regions within a presumptive envelope gene (Okamoto et al., 1992, Virology 190, 894-899; Ogata et al., 1991, Proc. Natl. Acad. Sci. USA 88, 3392-3396). In the present study, we analyzed three cases of hepatitis C virus infection, two in chimpanzees and one in humans, for the antigenicity of peptides predicted from the hypervariable region of viral RNA obtained during the follow-up. Our results showed a successive appearance of hepatitis C virus mutants with antigenically distinct amino acid sequence within the domain; and the amino acid replacement was associated with an alteration of predicted local secondary structure of the epitope region. Hence, the hypervariable domain of the hepatitis C virus envelope appeared to be structurally flexible and antigenically variable, providing the virus a way to escape from host immunity.