Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell Host Microbe. 2023 Mar 8;31(3):356-372.e5. doi: 10.1016/j.chom.2023.01.016. Epub 2023 Feb 20.
The decay kinetics of HIV-1-infected cells are critical to understand virus persistence. We evaluated the frequency of simian immunodeficiency virus (SIV)-infected cells for 4 years of antiretroviral therapy (ART). The intact proviral DNA assay (IPDA) and an assay for hypermutated proviruses revealed short- and long-term infected cell dynamics in macaques starting ART ∼1 year after infection. Intact SIV genomes in circulating CD4T cells showed triphasic decay with an initial phase slower than the decay of the plasma virus, a second phase faster than the second phase decay of intact HIV-1, and a stable third phase reached after 1.6-2.9 years. Hypermutated proviruses showed bi- or mono-phasic decay, reflecting different selective pressures. Viruses replicating at ART initiation had mutations conferring antibody escape. With time on ART, viruses with fewer mutations became more prominent, reflecting decay of variants replicating at ART initiation. Collectively, these findings confirm ART efficacy and indicate that cells enter the reservoir throughout untreated infection.
HIV-1 感染细胞的衰减动力学对于理解病毒持续性至关重要。我们评估了抗逆转录病毒治疗（ART） 4 年内感染猴免疫缺陷病毒（SIV）的细胞频率。完整原病毒 DNA 测定法（IPDA）和高突变原病毒测定法揭示了在感染后约 1 年开始 ART 的猕猴中短期和长期感染细胞动力学。在循环 CD4T 细胞中，完整的 SIV 基因组显示出三相衰减，初始阶段比血浆病毒的衰减更慢，第二阶段比完整 HIV-1 的第二阶段衰减更快，并且在 1.6-2.9 年后达到稳定的第三阶段。高突变原病毒显示出双相或单相衰减，反映了不同的选择压力。在 ART 起始时复制的病毒具有赋予抗体逃逸的突变。随着 ART 时间的推移，具有较少突变的病毒变得更加突出，反映了在 ART 起始时复制的变异体的衰减。总之，这些发现证实了 ART 的疗效，并表明细胞在未经治疗的感染过程中进入了储存库。
