Kim E Y, Winters M A, Kagan R M, Merigan T C
Center for AIDS Research, Stanford University, Stanford, California 94305-5107, USA.
J Virol. 2001 Nov;75(22):11227-33. doi: 10.1128/JVI.75.22.11227-11233.2001.
Twenty-four of over 24,000 patients genotyped over the past 3 years were found to have human immunodeficiency virus (HIV) isolates that possess an insert in the protease gene. In this report, we evaluated the spectrum of protease gene insertion mutations in patient isolates and analyzed the effect of these various insertion mutations on viral phenotypes. The inserts were composed of 1, 2, 5, or 6 amino acids that mapped at or between codons 35 and 38, 17 and 18, 21 and 25, or 95 and 96. Reduced susceptibility to protease inhibitors was found in isolates which possess previously reported drug resistance mutations. Fitness assays, including replication and competition experiments, showed that most of the isolates with inserts grew somewhat better than their counterparts with a deletion of the insert. These experiments demonstrate that, rarely, insertion mutations can develop in the HIV type 1 protease gene, are no more resistant than any other sequences which have similar associated resistance mutations, and can provide a borderline advantage in replication.
在过去3年对超过24000名患者进行基因分型的过程中，发现有24名患者的人类免疫缺陷病毒（HIV）分离株在蛋白酶基因中存在插入情况。在本报告中，我们评估了患者分离株中蛋白酶基因插入突变的范围，并分析了这些不同插入突变对病毒表型的影响。插入片段由1、2、5或6个氨基酸组成，定位于密码子35和38之间、17和18之间、21和25之间或95和96之间。在具有先前报道的耐药突变的分离株中发现对蛋白酶抑制剂的敏感性降低。包括复制和竞争实验在内的适应性测定表明，大多数有插入片段的分离株比其插入片段缺失的对应物生长得略好。这些实验表明，HIV-1蛋白酶基因中很少会出现插入突变，其耐药性并不比具有类似相关耐药突变的任何其他序列更强，并且在复制方面可提供一定的边缘优势。
