Yamaguchi K, Byrn R A
Division of Hematology/Oncology, Deaconess Hospital, Harvard Medical School, Boston, MA 02215, USA.
Biochim Biophys Acta. 1995 Dec 6;1253(2):136-40. doi: 10.1016/0167-4838(95)00167-1.
Proteinase inhibitors are an important new class of antiviral agents for AIDS, however, in vitro experiments have identified proteinase mutations that confer resistance to several different families of the inhibitors. This study was undertaken to determine if these resistance-conferring amino-acid substitutions occur in HIV strains before the application of selective pressure. We determined the nucleic acid sequence of the proteinase gene from the 23 clinical isolates of HIV-1 and three laboratory-adapted strains using a method that detects the majority species present in viral populations. Analysis of minor subpopulations will require alternative strategies. The clinical isolates studied contained an average of 3 (range 1-8) amino-acid substitutions as compared to the prototypical BH10 sequence. We did not detect substitutions characteristic of reported highly proteinase-resistant strains. These results suggest significant variation occurs in the HIV-1 proteinase gene but pre-existing highly proteinase-resistant strains are uncommon.
蛋白酶抑制剂是一类重要的新型抗艾滋病病毒药物，然而，体外实验已鉴定出一些蛋白酶突变，这些突变可使病毒对几种不同家族的抑制剂产生耐药性。本研究旨在确定这些赋予耐药性的氨基酸替代是否在施加选择压力之前就已出现在HIV毒株中。我们使用一种能够检测病毒群体中主要毒株的方法，测定了23株HIV-1临床分离株和3株实验室适应株的蛋白酶基因核酸序列。对次要亚群的分析需要采用其他策略。与原型BH10序列相比，所研究的临床分离株平均含有3个（范围为1至8个）氨基酸替代。我们未检测到已报道的高度蛋白酶耐药毒株所特有的替代。这些结果表明，HIV-1蛋白酶基因存在显著变异，但预先存在的高度蛋白酶耐药毒株并不常见。
