A structurally flexible and antigenically variable N-terminal domain of the hepatitis C virus E2/NS1 protein: implication for an escape from antibody.
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.
Taniguchi
S
S
Institute of Applied Biochemistry, University of Tsukuba, Ibaragi, Japan.
Okamoto
H
H
Sakamoto
M
M
Kojima
M
M
Tsuda
F
F
Tanaka
T
T
Munekata
E
E
Muchmore
E E
EE
Peterson
D A
DA
Mishiro
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000940:Antigenic Variation; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006508:Hepatitis Antibodies / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D002679:Pan troglodytes; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
D000956:Antigens, Viral; D000939:Epitopes; D006508:Hepatitis Antibodies; D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens