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首页> 美国卫生研究院文献>Journal of Clinical Microbiology >Unusual Naturally Occurring Humoral and Cellular Mutated Epitopes of Hepatitis B Virus in a Chronically Infected Argentine Patient with Anti-HBs Antibodies
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Unusual Naturally Occurring Humoral and Cellular Mutated Epitopes of Hepatitis B Virus in a Chronically Infected Argentine Patient with Anti-HBs Antibodies

机译：乙型肝炎病毒的慢性感染阿根廷患者中乙型肝炎病毒的异常自然发生的体液和细胞突变表位

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Serum hepatitis B virus (HBV) DNA was extracted from a chronically infected patient with cocirculation of hepatitis B surface antigen (HBsAg) and anti-HBs antibodies. Direct PCR and clone-derived sequences of the S and overlapped P genes were obtained. DNA sequences and phylogenetic analysis ascribed this isolate to genotype A (serotype adw2). Five of six HBV DNA clones exhibited point mutations inside and outside the major hydrophilic region, while the sixth clone exhibited a genotype A “wild-type” amino acid sequence. Observed replacements included both humoral and/or cellular (major histocompatibility complex class I [MHC-I] and MHC-II) HBV mutated epitopes, such as S45A, P46H, L49H, C107R, T125A, M133K, I152F, P153T, T161S, G185E, A194T, G202R, and I213L. None of these mutants were individually present within a given clone. The I213L replacement was the only one observed in the five clones carrying nonsynonymous mutations in the S gene. Some of the amino acid substitutions are reportedly known to be responsible for the emergence of immune escape mutants. C107R replacement prevents disulfide bonding, thus disrupting the first loop of the HBsAg. Circulation of some of these mutants may represent a potential risk for the community, since neither current hepatitis B vaccines nor hyperimmune hepatitis B immune globulin are effectively prevent the liver disease thereto associated. Moreover, some of the recorded HBsAg variants may influence the accuracy of the results obtained with currently used diagnostic tests.
机译：从具有乙肝表面抗原（HBsAg）和抗HBs抗体共同循环的慢性感染患者中提取血清乙肝病毒（HBV）DNA。获得了S和重叠P基因的直接PCR和克隆衍生的序列。 DNA序列和系统发育分析将这种分离物归因于基因型A（血清型adw2）。六个HBV DNA克隆中的五个在主要亲水区域的内部和外部均表现出点突变，而第六个克隆则显示出基因型A“野生型”氨基酸序列。观察到的替代品包括体液和/或细胞性（主要组织相容性复合物I类[MHC-I]和MHC-II类）HBV突变的抗原决定簇，例如S45A，P46H，L49H，C107R，T125A，M133K，I152F，P153T，T161S，G185E ，A194T，G202R和I213L。这些突变体中没有一个单独存在于给定的克隆中。 I213L置换是在S基因中携带非同义突变的五个克隆中唯一观察到的一个。据报道，某些氨基酸取代是导致免疫逃逸突变体出现的原因。更换C107R可以防止二硫键，从而破坏HBsAg的第一个环。由于目前的乙型肝炎疫苗和超免疫性乙型肝炎免疫球蛋白均不能有效地预防与其相关的肝病，因此其中一些突变体的流通可能对社区构成潜在风险。此外，某些已记录的HBsAg变异可能会影响通过当前使用的诊断测试获得的结果的准确性。

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