Nainan O V, Brinton M A, Margolis H S
Hepatitis Branch, Centers for Disease Control (World Health Organization Collaborating Centre for Research and Reference in Viral Hepatitis), Atlanta, Georgia 30333.
Virology. 1992 Dec;191(2):984-7. doi: 10.1016/0042-6822(92)90277-v.
Antigenic mutants of human hepatitis A virus (human-HAV) were isolated by their resistance to neutralizing monoclonal antibodies raised to human-HAV. The nucleotide sequence determined for the capsid regions of 12 mutants identified amino acid changes that clustered in three non-overlapping sites; one in VP3 and two in VP1. All mutants had a change at amino acid residue 70 in VP3, indicating its primary importance for antibody binding. Ten mutants had two amino acid changes occurring in the VP3 site as well as one in one of the two VP1 sites. These data suggest that both sites in VP1 interact with the single VP3 site to form the immunodominant epitope of HAV. The amino acid changes found in the antigenic mutants of human-HAV selected in this study were located in the same positions as changes found in strains of HAV isolated from Old World monkeys. These simian strains of HAV are not recognized by most monoclonal antibodies raised to human-HAV, suggesting that the observed amino acid changes are part of the antibody binding site.
通过对人甲型肝炎病毒（human - HAV）产生的中和单克隆抗体具有抗性，分离出了人甲型肝炎病毒的抗原突变体。对12个突变体的衣壳区域测定的核苷酸序列确定了聚集在三个不重叠位点的氨基酸变化；一个在VP3中，两个在VP1中。所有突变体在VP3的氨基酸残基70处都有变化，表明其对抗体结合至关重要。十个突变体在VP3位点有两个氨基酸变化，并且在两个VP1位点之一也有一个变化。这些数据表明，VP1中的两个位点与单个VP3位点相互作用以形成HAV的免疫显性表位。在本研究中选择的人甲型肝炎病毒抗原突变体中发现的氨基酸变化位于与从旧世界猴分离的甲型肝炎病毒株中发现的变化相同的位置。这些猿猴甲型肝炎病毒株不被大多数针对人甲型肝炎病毒产生的单克隆抗体识别，这表明观察到的氨基酸变化是抗体结合位点的一部分。
