Taniguchi S, Okamoto H, Sakamoto M, Kojima M, Tsuda F, Tanaka T, Munekata E, Muchmore E E, Peterson D A, Mishiro S
Institute of Applied Biochemistry, University of Tsukuba, Ibaragi, Japan.
Virology. 1993 Jul;195(1):297-301. doi: 10.1006/viro.1993.1378.
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.
丙型肝炎病毒在大多数受感染宿主中持续存在，并在人类中引发慢性肝炎、肝硬化和/或肝细胞癌。在感染过程中，丙型肝炎病毒的RNA基因组在假定包膜基因内的一个或两个“高变”区域频繁发生错义突变（冈本等人，1992年，《病毒学》190卷，894 - 899页；绪方等人，1991年，《美国国家科学院院刊》88卷，3392 - 3396页）。在本研究中，我们分析了三例丙型肝炎病毒感染病例，两例发生在黑猩猩身上，一例发生在人类身上，分析了随访期间从病毒RNA高变区域预测的肽段的抗原性。我们的结果显示，在该结构域内相继出现了具有抗原性不同氨基酸序列的丙型肝炎病毒突变体；并且氨基酸替换与表位区域预测的局部二级结构改变有关。因此，丙型肝炎病毒包膜的高变结构域似乎在结构上具有灵活性且在抗原性上具有变异性，为病毒提供了一种逃避宿主免疫的方式。
