Multiple Origins of Virus Persistence during Natural Control of HIV Infection.
Multiple Origins of Virus Persistence during Natural Control of HIV Infection.
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DOI：
10.1016/j.cell.2016.06.039
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发表时间：
2016-08-11
期刊：
影响因子：
64.5
通讯作者：
Douek DC
中科院分区：
文献类型：
--
作者：
Boritz EA;Darko S;Swaszek L;Wolf G;Wells D;Wu X;Henry AR;Laboune F;Hu J;Ambrozak D;Hughes MS;Hoh R;Casazza JP;Vostal A;Bunis D;Nganou-Makamdop K;Lee JS;Migueles SA;Koup RA;Connors M;Moir S;Schacker T;Maldarelli F;Hughes SH;Deeks SG;Douek DC
有针对性的艾滋病毒治疗策略需要定义维持病毒的机制。在这里，我们通过对病毒、T细胞受体基因、HIV整合位点和细胞转录组进行测序，追踪了具有自然病毒控制的个体中HIV复制和感染的CD4 T细胞的持续性。我们的研究结果揭示了三种机制的艾滋病毒持久性不同的解剖和功能隔室内运作。在淋巴结中，我们在T滤泡辅助细胞（TFH）和非TFH记忆细胞中检测到具有主动复制的遗传和转录属性的病毒。在血液中，我们检测到诱导型前病毒的档案来源高度分化，克隆扩增的细胞。连接淋巴结和血液的是一小群携带近期来源的诱导型前病毒的循环细胞。因此，HIV在淋巴组织中的复制、感染细胞的克隆扩增和最近感染细胞的再循环共同作用，以维持HIV控制者中的病毒，尽管存在有效的抗病毒免疫。HIV在能够自发控制感染的人群中的持续存在涉及不同的解剖和功能分区内的不同机制。
Targeted HIV cure strategies require definition of the mechanisms that maintain the virus. Here, we tracked HIV replication and the persistence of infected CD4 T cells in individuals with natural virologic control by sequencing viruses, T cell receptor genes, HIV integration sites and cellular transcriptomes. Our results revealed three mechanisms of HIV persistence operating within distinct anatomic and functional compartments. In lymph node, we detected viruses with genetic and transcriptional attributes of active replication in both T follicular helper (TFH) cells and non-TFH memory cells. In blood, we detected inducible proviruses of archival origin among highly differentiated, clonally expanded cells. Linking the lymph node and blood was a small population of circulating cells harboring inducible proviruses of recent origin. Thus, HIV replication in lymphoid tissue, clonal expansion of infected cells, and recirculation of recently infected cells act together to maintain the virus in HIV controllers despite effective antiviral immunity. HIV persistence in people who can spontaneously control the infection involves different mechanisms within distinct anatomic and functional compartments.