Ledwaba Johanna, Sayed Yasien, Pillay Visva, Morris Lynn, Hunt Gillian
1 Centre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg, South Africa.
2 Protein Structure-Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa.
AIDS Res Hum Retroviruses. 2019 Jul;35(7):673-678. doi: 10.1089/AID.2019.0012. Epub 2019 Apr 4.
Human immunodeficiency virus-1 (HIV-1) protease sequences from 2,225 protease inhibitor (PI)-naïve HIV-1 subtype C-infected individuals collected over a 14-year period were analyzed for polymorphisms. Over 50% of sequences differed from an HIV-1 subtype B consensus sequence at 8 of the 99 amino acids at residues 12, 15, 19, 36, 41, 69, 89, and 93, but not in the functionally important regions. The frequency of primary resistance and accessory mutations occurred in <1% of the sequences. Of note, 11 sequences (0.5%) harbored amino acid insertions between residues 36 and 39, located in the elbow of the flap region. The insertions were found throughout the 13-year period. Occurrence of insertions in subtype C viruses is rare and viruses remain sensitive to currently used PIs (lopinavir/r, atazanavir/r, and darunavir/r). However, ongoing characterization of isolates is required to identify changes that may impact PI treatment since PIs are part of standard SA regimens.
对在14年期间收集的2225名未接受过蛋白酶抑制剂（PI）治疗的HIV-1 C亚型感染个体的人类免疫缺陷病毒1型（HIV-1）蛋白酶序列进行多态性分析。超过50%的序列在第12、15、19、36、41、69、89和93位的99个氨基酸中有8个与HIV-1 B亚型共有序列不同，但不在功能重要区域。主要耐药突变和辅助突变的频率在<1%的序列中出现。值得注意的是，11个序列（0.5%）在位于瓣区肘部的第36和39位残基之间存在氨基酸插入。这些插入在整个13年期间都有发现。C亚型病毒中插入的情况很少见，并且病毒对目前使用的蛋白酶抑制剂（洛匹那韦/利托那韦、阿扎那韦/利托那韦和达芦那韦/利托那韦）仍敏感。然而，由于蛋白酶抑制剂是标准抗逆转录病毒治疗方案的一部分，因此需要对分离株进行持续的特征分析，以识别可能影响蛋白酶抑制剂治疗的变化。
