King R W, Winslow D L, Garber S, Scarnati H T, Bachelor L, Stack S, Otto M J
DuPont Merck Pharmaceutical Company, Glenolden, PA 19036, USA.
Antiviral Res. 1995 Sep;28(1):13-24. doi: 10.1016/0166-3542(95)00033-i.
The HIV-1 protease (PR) is essential for the production of mature virions. As such, it has become a target for the development of anti-HIV chemotherapeutics. Multiple passages of virus in cell culture in the presence of PR inhibitors have resulted in the selection of variants with decreased sensitivity to inhibitors of the PR. The most common alteration observed is a single amino acid change at position 82. This particular position has been well characterized by several laboratories as being important for the susceptibility of the virus to inhibitors of PR function. Mutations which result in the substitution of the wild-type valine with alanine, phenylalanine, threonine or isoleucine at position 82 of the PR have been associated with decreased sensitivity to several PR inhibitors. We describe here a clinical strain of HIV-1 that contains an isoleucine at position 82 of the PR instead of the usual valine. This strain is unique in that it was isolated from a patient that was anti-retroviral naive, and in the past, variants at position 82 of the PR have only been found after treatment of patients or cell culture with PR inhibitors. Moreover, this virus remains sensitive to PR inhibitors of the cyclic urea and C-2 symmetrical diol classes.
HIV-1蛋白酶（PR）对于成熟病毒体的产生至关重要。因此，它已成为抗HIV化疗药物开发的靶点。在PR抑制剂存在的情况下，病毒在细胞培养中多次传代导致了对PR抑制剂敏感性降低的变异体的选择。观察到的最常见变化是第82位的单个氨基酸改变。几个实验室已充分证明这个特定位置对于病毒对PR功能抑制剂的敏感性很重要。在PR的第82位导致野生型缬氨酸被丙氨酸、苯丙氨酸、苏氨酸或异亮氨酸取代的突变与对几种PR抑制剂的敏感性降低有关。我们在此描述一种HIV-1临床毒株，其PR的第82位含有异亮氨酸而非通常的缬氨酸。该毒株的独特之处在于它是从一名未经抗逆转录病毒治疗的患者中分离出来的，而且过去仅在患者接受PR抑制剂治疗或细胞培养后才在PR的第82位发现变异体。此外，这种病毒对环脲类和C-2对称二醇类PR抑制剂仍然敏感。
