Luk K C, Kaptué L, Zekeng L, Soriano V, Gürtler L, Devare S G, Schochetman G, Hackett J
AIDS Research and Retrovirus Discovery, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
AIDS Res Hum Retroviruses. 2001 Nov 1;17(16):1555-61. doi: 10.1089/08892220152644269.
Mutations within the protease gene associated with reduced susceptibility to protease inhibitors have been well documented for HIV-1 group M subtype B strains. In contrast, limited genotypic and phenotypic information is available for the genetically diverse HIV-1 group O strains. Preexisting resistance-associated polymorphisms have the potential to contribute to a poor virological response to antiviral drug treatment in group O-infected patients. In the present study, the protease genes of 28 protease inhibitor-naive HIV-1 group O-infected patients were analyzed to identify any naturally occurring amino acid polymorphisms associated with drug resistance. Comparison of the consensus group O protease sequence with subtype B of group M indicated that both groups have almost identical sequences in the protease active site, the flap and the substrate-binding site. Analysis of the 28 individual protease sequences revealed polymorphisms at 34% of the positions within the protease gene, but no primary mutations associated with protease inhibitor resistance. In contrast, each of the strains harbored multiple secondary or accessory mutations associated with resistance to protease inhibitors in group M viruses. Residues 10I, 15V, 36I, 41K, 62V, 63T/A/K/I, 64V, 71V, and 93L were identified in most strains. The presence of multiple natural sequence polymorphisms associated with drug resistance in the protease gene of group O viruses may contribute to a more rapid emergence of drug resistance phenotype and treatment failure in group O-infected patients.
与蛋白酶抑制剂敏感性降低相关的蛋白酶基因突变在HIV-1 M组B亚型毒株中已有充分记录。相比之下，关于基因多样的HIV-1 O组毒株的基因型和表型信息有限。预先存在的耐药相关多态性可能导致O组感染患者对抗病毒药物治疗的病毒学反应不佳。在本研究中，对28例未接受过蛋白酶抑制剂治疗的HIV-1 O组感染患者的蛋白酶基因进行了分析，以确定任何与耐药相关的自然发生的氨基酸多态性。O组蛋白酶共有序列与M组B亚型的比较表明，两组在蛋白酶活性位点、瓣片和底物结合位点的序列几乎相同。对28个个体蛋白酶序列的分析揭示了蛋白酶基因内34%的位置存在多态性，但没有与蛋白酶抑制剂耐药相关的主要突变。相比之下，每个毒株都含有多个与M组病毒中蛋白酶抑制剂耐药相关的次要或辅助突变。在大多数毒株中鉴定出10I、15V、36I、41K、62V、63T/A/K/I、64V、71V和93L位点的残基。O组病毒蛋白酶基因中存在多个与耐药相关的自然序列多态性，可能导致O组感染患者耐药表型更快出现和治疗失败。
