Kummet Nathan, Mishra Neha, Diaz Adela, Cusick Nicholas, Klotz Stephen, Ahmad Nafees
Department of Immunobiology, College of Medicine, University of Arizona, Tucson, Arizona, USA.
Department of Medicine, College of Medicine, University of Arizona, Tucson, Arizona, USA.
AIDS Res Hum Retroviruses. 2025 Mar;41(3):143-154. doi: 10.1089/aid.2024.0029. Epub 2024 Dec 26.
Despite advancements in antiretroviral therapy (ART) that reduces the viral load to undetectable levels and improve CD4 T cell counts, viral eradication has not been achieved due to HIV-1 persistence in resting CD4 T-cells. We, therefore, characterized the gene, which is essential for HIV-1 replication and pathogenesis, from 20 virologically controlled aging individuals with HIV (HIV) on long-term ART and improved CD4 T-cell counts, with a particular focus on older individuals. Peripheral blood mononuclear cell genomic DNA from HIV were used to amplify gene by polymerase chain reaction followed by nucleotide sequencing and analysis. Phylogenetic analysis showed that each HIV sequences were confined to their own subtrees and well discriminated from other HIV sequences. Moreover, there was a low degree of viral heterogeneity and lower estimates of genetic diversity within these individuals' sequences, which decreased with increasing CD4 T counts in these HIV. Most HIV Tat deduced amino acid sequences showed intact open reading frames and maintained the important functional domains for Tat functions, including transactivation, TAR binding, and nuclear localization. Furthermore, Tat-deduced amino acid sequences showed variation in previously characterized cytotoxic T lymphocytes (CTL) epitopes, suggesting escape mutants. In conclusion, a low degree of genetic variability and conservation of functional domains and variations in CTL epitopes were the features of sequences that may be contributing to viral persistence in these 20 aging individuals with HIV on long-term ART.
尽管抗逆转录病毒疗法（ART）取得了进展，可将病毒载量降低到检测不到的水平并提高CD4 T细胞计数，但由于HIV-1在静息CD4 T细胞中持续存在，尚未实现病毒根除。因此，我们对20名接受长期ART且CD4 T细胞计数有所改善的病毒学控制的老年HIV感染者（HIV）中对HIV-1复制和发病机制至关重要的基因进行了表征，特别关注老年个体。利用HIV感染者的外周血单核细胞基因组DNA，通过聚合酶链反应扩增该基因，随后进行核苷酸测序和分析。系统发育分析表明，每个HIV序列都局限于其自己的子树，并且与其他HIV序列有很好的区分。此外，这些个体的序列中病毒异质性程度较低，遗传多样性估计值也较低，在这些HIV感染者中，随着CD4 T细胞计数的增加而降低。大多数HIV Tat推导的氨基酸序列显示完整的开放阅读框，并保留了Tat功能的重要功能域，包括反式激活、TAR结合和核定位。此外，Tat推导的氨基酸序列在先前表征的细胞毒性T淋巴细胞（CTL）表位中显示出变异，提示存在逃逸突变体。总之，低程度的遗传变异性、功能域的保守性以及CTL表位的变异是这些序列的特征，可能有助于这20名长期接受ART治疗的老年HIV感染者体内病毒的持续存在。
