Mosebi Salerwe, Morris Lynn, Dirr Heini W, Sayed Yasien
Protein Structure-Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand, I Jan Smuts Avenue, Johannesburg 2050, South Africa.
J Virol. 2008 Nov;82(22):11476-9. doi: 10.1128/JVI.00726-08. Epub 2008 Sep 3.
Human immunodeficiency virus (HIV) infections in sub-Saharan Africa represent about 56% of global infections. Study of active-site mutations (the V82A single mutation and the V82F I84V double mutation) in the less-studied South African HIV type 1 subtype C (C-SA) protease indicated that neither mutation had a significant impact on the proteolytic functioning of the protease. However, the binding affinities of, and inhibition by, saquinavir, ritonavir, indinavir, and nelfinavir were weaker for each variant than for the wild-type protease, with the double mutant exhibiting the most dramatic change. Therefore, our results show that the C-SA V82F I84V double mutation decreased the binding affinities of protease inhibitors to levels significantly lower than that required for effective inhibition.
撒哈拉以南非洲地区的人类免疫缺陷病毒（HIV）感染病例约占全球感染病例的56%。对研究较少的南非1型C亚型HIV（C-SA）蛋白酶活性位点突变（V82A单突变和V82F I84V双突变）的研究表明，这两种突变对蛋白酶的蛋白水解功能均无显著影响。然而，与野生型蛋白酶相比，沙奎那韦、利托那韦、茚地那韦和奈非那韦对每种变体的结合亲和力及抑制作用都较弱，其中双突变体表现出最显著的变化。因此，我们的研究结果表明，C-SA V82F I84V双突变使蛋白酶抑制剂的结合亲和力降至显著低于有效抑制所需水平。
