Although many HIV-infected patients have attained older age owing to the success of antiretroviral therapy (ART) in controlling viremia and increasing CD4 T cell counts, HIV continues to persist in several target cells. We have characterized 514 HIV-1 envelope V3 region sequences (94–96 amino acids [aa]) from 25 HIV-infected older patients' peripheral blood mononuclear cell DNA on long-term ART with controlled viremia (undetectable viral load) and improved CD4 T cell counts. Phylogenetic analysis revealed that the V3 region sequences of each patient formed distinct clusters that were well separated and discriminated from other patients' sequences. The coding potential of the V3 region, including several patient-specific amino acid motifs and functional domains, including the two cysteines sandwiching the V3 loop, the central GPGR motif with variation at one position in some sequences, the base GDIR motif, and the N-glycosylation sites were generally conserved. The patients' V3 region sequences contained amino acid motifs conferring affinity mostly for CCR5 coreceptor, suggesting R5 phenotype. There was a low degree of heterogeneity and lower estimates of genetic diversity in all 25 patients' V3 region sequences. Twelve of 25 patients' V3 region sequences were found to be under positive selection pressure. Analysis of the several cytotoxic T lymphocytes (CTL) epitopes showed variation, whereas some of known neutralizing antibodies (nAbs) epitopes showed conservation in patients' V3 region sequences. In conclusion, a low degree of genetic variability and maintenance of functional domains with R5 phenotypes, and variation in CTL and conservation of nAb epitopes were the hallmarks of V3 region sequences from our 25 virologically controlled HIV-infected older patients on long-term ART.

中文翻译：

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长期抗逆转录病毒治疗的受病毒控制的 HIV 感染老年患者的 HIV-1 包络 V3 区域序列的表征

尽管由于抗逆转录病毒疗法 (ART) 在控制病毒血症和增加 CD4 T 细胞计数方面取得成功，许多 HIV 感染患者已达到高龄，但 HIV 继续存在于几个靶细胞中。我们已经表征了 514 个 HIV-1 包膜 V3 区序列（94-96 个氨基酸 [aa]），这些序列来自 25 名感染 HIV 的老年患者的外周血单核细胞 DNA，在长期 ART 中，病毒血症得到控制（病毒载量无法检测）和 CD4 改善T 细胞计数。系统发育分析表明，每个患者的 V3 区序列形成了不同的簇，这些簇与其他患者的序列很好地分离和区分。V3 区的编码潜力，包括几个患者特异性氨基酸基序和功能域，包括夹在 V3 环中间的两个半胱氨酸，N-糖基化位点通常是保守的。患者的 V3 区序列包含赋予主要对 CCR5 辅助受体亲和力的氨基酸基序，表明 R5 表型。在所有 25 名患者的 V3 区序列中，存在低程度的异质性和较低的遗传多样性估计。发现 25 名患者的 V3 区序列中有 12 名处于正选择压力之下。对几种细胞毒性 T 淋巴细胞 (CTL) 表位的分析显示出变异，而一些已知的中和抗体 (nAb) 表位在患者的 V3 区序列中显示出保守性。总之，具有 R5 表型的功能域的低程度遗传变异和维持，