Infectivity and pathogenicity in chimpanzees of a surface gene mutant of hepatitis B virus that emerged in a vaccinated infant
Infectivity and pathogenicity in chimpanzees of a surface gene mutant of hepatitis B virus that emerged in a vaccinated infant
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DOI：
10.1093/infdis/175.3.511
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发表时间：
1997-03-01
影响因子：
6.4
通讯作者：
Purcell, RH
中科院分区：
文献类型：
--
作者：
Ogata, N;Zanetti, AR;Purcell, RH
乙肝病毒主要表面蛋白a表位氨基酸发生突变的变异株已被鉴定，并对其生物学特性提出了质疑。将S基因第145位密码子精氨酸替换为甘氨酸的首例乙肝病毒变异株血清，接种到6只血清阴性黑猩猩体内。其中5只动物出现了乙肝的血清学和/或生化证据。基于聚合酶链式反应的分析区分了野生型和变异型病毒基因组，发现在指数血清的10(-6)和10(-7)稀释度中存在纯种群的变异型基因组，导致只接受这些稀释物的黑猩猩感染变异型病毒。突变病毒的克隆在体外转染法中复制正常。因此，这种乙肝病毒表面基因突变体在黑猩猩体内是活的、有感染性的和致病性的。
Hepatitis B virus (HBV) variants with amino acid mutations in the a epitope of the major surface protein have been identified, and questions have been raised regarding their biologic properties. Dilutions of serum that contained the first such described HBV mutant, with an Arg-for-Gly substitution at codon 145 of the S gene, were inoculated into 6 seronegative chimpanzees. Five of the animals developed serologic and/or biochemical evidence of hepatitis B. A polymerase chain reaction-based assay that discriminated between the wild type and mutant viral genomes revealed that a pure population of the mutant genome was present in the 10(-6) and 10(-7) dilutions of the index serum, resulting in infection of the chimpanzees receiving these dilutions only with the mutant virus. A clone of the mutant virus replicated normally following transfection in vitro. Thus, this HBV surface gene mutant is viable, infectious, and pathogenic in chimpanzees.