Lech W J, Wang G, Yang Y L, Chee Y, Dorman K, McCrae D, Lazzeroni L C, Erickson J W, Sinsheimer J S, Kaplan A H
Department of Medicine, University of California at Los Angeles 90024, USA.
J Virol. 1996 Mar;70(3):2038-43. doi: 10.1128/JVI.70.3.2038-2043.1996.
We have evaluated the sequence diversity of the protease human immunodeficiency virus type 1 in vivo. Our analysis of 246 protease coding domain sequences obtained from 12 subjects indicates that amino acid substitutions predicted to give rise to protease inhibitor resistance may be present in patients who have not received protease inhibitors. In addition, we demonstrated that amino acid residues directly involved in enzyme-substrate interactions may be varied in infected individuals. Several of these substitutions occurred in combination either more or less frequently than would be expected if their appearance was independent, suggesting that one substitution may compensate for the effects of another. Taken together, our analysis indicates that the human immunodeficiency virus type 1 protease has flexibility sufficient to vary critical subsites in vivo, thereby retaining enzyme function and viral pathogenicity.
我们评估了人类免疫缺陷病毒1型蛋白酶在体内的序列多样性。我们对从12名受试者获得的246个蛋白酶编码域序列进行的分析表明，在未接受蛋白酶抑制剂治疗的患者中可能存在预计会导致蛋白酶抑制剂耐药性的氨基酸替代。此外，我们证明了在受感染个体中，直接参与酶-底物相互作用的氨基酸残基可能会有所不同。这些替代中的几种组合出现的频率或多或少高于其出现是独立情况时的预期频率，这表明一种替代可能会补偿另一种替代的影响。综合来看，我们的分析表明，人类免疫缺陷病毒1型蛋白酶具有足够的灵活性，能够在体内改变关键亚位点，从而保持酶的功能和病毒的致病性。
