Nolan David J, Rose Rebecca, Rodriguez Patricia H, Salemi Marco, Singer Elyse J, Lamers Susanna L, McGrath Michael S
1 BioInfoExperts LLC , Thibodaux, Louisiana.
2 Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, Florida.
AIDS Res Hum Retroviruses. 2018 Jan;34(1):123-125. doi: 10.1089/AID.2017.0254. Epub 2017 Nov 30.
Combined antiretroviral therapy (cART) does not eradicate HIV, which persists for years and can re-establish replication if treatment is stopped. The current challenge is identifying those tissues harboring virus through cART. Here, we used HIV env-nef single genome sequencing and HIV gag droplet digital PCR (ddPCR) to survey 50 tissues from five subjects on cART with no detectable plasma viral load at death. The spleen most consistently contained multiple proviral and expressed sequences (4/5 participants). Spleen-derived HIV demonstrated two distinct phylogenetic patterns: multiple identical sequences, often from different tissues, as well as diverse viral sequences on long terminal branches. Our results suggested that ddPCR may overestimate the size of the tissue-based viral reservoir. The spleen, a lymphatic organ at the intersection of the immune and circulatory systems, may play a key role in viral persistence.
联合抗逆转录病毒疗法（cART）无法根除HIV，HIV会持续存在数年，并且如果停止治疗，病毒会重新建立复制。当前的挑战是通过cART识别那些藏匿病毒的组织。在这里，我们使用HIV env-nef单基因组测序和HIV gag液滴数字PCR（ddPCR）对5名接受cART治疗且死亡时血浆病毒载量检测不到的受试者的50个组织进行了调查。脾脏最一致地含有多个前病毒和表达序列（5名参与者中有4名）。源自脾脏的HIV表现出两种不同的系统发育模式：多个相同序列，通常来自不同组织，以及长末端分支上的多样化病毒序列。我们的结果表明，ddPCR可能高估了基于组织的病毒库的大小。脾脏是免疫和循环系统交汇处的淋巴器官，可能在病毒持续存在中起关键作用。
