Watkins B A, Reitz M S, Wilson C A, Aldrich K, Davis A E, Robert-Guroff M
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland 20892.
J Virol. 1993 Dec;67(12):7493-500. doi: 10.1128/JVI.67.12.7493-7500.1993.
Sera from many HIV-1-infected individuals contain broadly reactive, specific neutralizing antibodies. Despite their broad reactivity, variant viruses, resistant to neutralization, can be selected in vitro in the presence of such antisera. We have previously shown that neutralization resistance of an escape mutant with an amino acid substitution in the transmembrane protein (A582T) occurs because of alteration of a conformational epitope that is recognized by neutralizing antibodies directed against the CD4 binding site. In this report we demonstrate that immune escape via a single-amino-acid substitution (A281V) within a conserved region of the envelope glycoprotein gp120 confers neutralization resistance against a broadly reactive neutralizing antiserum from a seropositive individual. We show this alteration affects V3 and additional regions unrelated to V3 or the CD4 binding site. Together with previous studies on escape mutants selected in vitro, our findings suggest that immune-selective pressure can arise by multiple pathways.
许多感染HIV-1的个体血清中含有广泛反应性的特异性中和抗体。尽管这些抗体具有广泛反应性，但在存在此类抗血清的情况下，仍可在体外筛选出对中和作用具有抗性的变异病毒。我们之前已经表明，跨膜蛋白中发生氨基酸取代（A582T）的逃逸突变体产生中和抗性，是因为针对CD4结合位点的中和抗体所识别的构象表位发生了改变。在本报告中，我们证明包膜糖蛋白gp120保守区域内的单氨基酸取代（A281V）导致的免疫逃逸赋予了对一名血清阳性个体的广泛反应性中和抗血清的中和抗性。我们表明这种改变影响V3以及与V3或CD4结合位点无关的其他区域。结合之前关于体外筛选出的逃逸突变体的研究，我们的发现表明免疫选择压力可通过多种途径产生。
