Choi Jun Yong, Chaillon Antoine, Oh Jin Ok, Ahn Jin Young, Ann Hae Won, Jung In Young, Ahn Mi-Young, Jeon Yong Duk, Ku Nam Su, Smith Davey M, Kim June Myung
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
J Med Virol. 2016 Apr;88(4):606-13. doi: 10.1002/jmv.24375. Epub 2015 Sep 21.
The cellular source of HIV RNA circulating in blood plasma remains unclear. Here, we investigated whether sequence analysis of HIV RNA populations circulating before combination antiretroviral therapy (cART) and HIV DNA populations in cellular subsets (CS) after cART could identify the cellular sources of circulating HIV RNA. Blood was collected from five subjects at cART initiation and again 6 months later. Naïve CD4+ T cells, resting central memory and effector memory CD4+ T cells, activated CD4+ T cells, monocytes, and natural killer cells were sorted using a fluorescence-activated cell sorter. HIV-1 env C2V3 sequences from HIV RNA in blood plasma and HIV DNA in CSs were generated using single genome sequencing. Sequences were evaluated for viral compartmentalization (Fst test) and migration events (MEs; Slatkin Maddison and cladistic measures) between blood plasma and each CS. Viral compartmentalization was observed in 88% of all cellular subset comparisons (range: 77-100% for each subject). Most observed MEs were directed from blood plasma to CSs (52 MEs, 85.2%). In particular, there was only viral movement from plasma to NK cells (15 MEs), monocytes (seven MEs), and naïve cells (five ME). We observed a total of nine MEs from activated CD4 cells (2/9 MEs), central memory T cells (3/9 MEs), and effector memory T cells (4/9 MEs) to blood plasma. Our results revealed that the HIV RNA population in blood plasma plays an important role in seeding various cellular reservoirs and that the cellular source of the HIV RNA population is activated central memory and effector memory T cells.
血浆中循环的HIV RNA的细胞来源尚不清楚。在此，我们研究了在联合抗逆转录病毒疗法（cART）之前循环的HIV RNA群体的序列分析以及cART后细胞亚群（CS）中的HIV DNA群体的序列分析是否能够识别循环HIV RNA的细胞来源。在开始cART时从5名受试者采集血液，6个月后再次采集。使用荧光激活细胞分选仪对初始CD4 + T细胞、静息中央记忆和效应记忆CD4 + T细胞、活化CD4 + T细胞、单核细胞和自然杀伤细胞进行分选。使用单基因组测序生成血浆中HIV RNA和CS中HIV DNA的HIV-1 env C2V3序列。评估血浆与每个CS之间的病毒区室化（Fst检验）和迁移事件（MEs；Slatkin Maddison和分支测量）。在所有细胞亚群比较的88%中观察到病毒区室化（每个受试者范围：77 - 100%）。观察到的大多数MEs是从血浆指向CSs（52个MEs，85.2%）。特别是，仅存在从血浆到NK细胞（15个MEs）、单核细胞（7个MEs）和初始细胞（5个MEs）的病毒移动。我们总共观察到9个从活化CD4细胞（2/9个MEs）、中央记忆T细胞（3/9个MEs）和效应记忆T细胞（4/9个MEs）到血浆的MEs。我们的结果表明，血浆中的HIV RNA群体在播种各种细胞储存库中起重要作用，并且HIV RNA群体的细胞来源是活化的中央记忆和效应记忆T细胞。
