HIV Latency Is Established Directly and Early in Both Resting and Activated Primary CD4 T Cells.
HIV Latency Is Established Directly and Early in Both Resting and Activated Primary CD4 T Cells.
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DOI：
10.1371/journal.ppat.1004955
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发表时间：
2015-06
期刊：
影响因子：
6.7
通讯作者：
Verdin E
中科院分区：
文献类型：
--
作者：
Chavez L;Calvanese V;Verdin E
高效抗逆转录病毒疗法（HAART）将人类免疫缺陷病毒（HIV）复制抑制到无法检测的水平，但不能完全根除病毒，因为一小部分CD 4 + T细胞仍处于潜伏感染状态。由于HIV仅有效地感染活化的CD 4 + T细胞，并且由于潜伏的HIV主要存在于静息的CD 4 + T细胞中，因此通常假设当有效感染的细胞重新进入静息状态时，潜伏期建立，从而将病毒捕获在潜伏状态。在这项研究中，我们使用双报告病毒-HIV Duo-Fluo I，它在感染后立即识别潜伏感染的细胞，以研究T细胞活化如何影响HIV潜伏期的建立。我们表明，HIV潜伏期可以从静息和活化的CD 4 + T细胞的直接感染中产生。重要的是，将生产性感染的细胞恢复到静息状态与整合的HIV的显著沉默无关。我们进一步表明，与外周血相比，来自人淋巴组织（扁桃体，脾脏）的静息CD 4 + T细胞在感染后表现出增加的潜伏期。我们的研究结果提出了关于建立潜伏性HIV的最普遍接受的模型的重要问题，并表明静息和活化的初级CD 4 + T细胞的感染产生潜伏期。HIV潜伏期的研究一直受到阻碍，因为在体内很少有潜伏感染的细胞，我们不能区分潜伏感染的细胞和未感染的细胞之前，重新激活的潜伏前病毒。一般来说，HIV潜伏期通过在潜伏期建立后重新激活潜伏感染的细胞来定量研究。然而，这种做法限制了如何建立潜伏期和潜伏前病毒如何被重新激活的研究。我们最近开发的双报告病毒HIV Duo-Fluo I可以在感染后早期识别潜伏感染的细胞。在这项研究中，我们使用HIV Duo-Fluo I来研究T细胞活化如何影响HIV感染的结果。
Highly active antiretroviral therapy (HAART) suppresses human immunodeficiency virus (HIV) replication to undetectable levels but cannot fully eradicate the virus because a small reservoir of CD4+ T cells remains latently infected. Since HIV efficiently infects only activated CD4+ T cells and since latent HIV primarily resides in resting CD4+ T cells, it is generally assumed that latency is established when a productively infected cell recycles to a resting state, trapping the virus in a latent state. In this study, we use a dual reporter virus—HIV Duo-Fluo I, which identifies latently infected cells immediately after infection—to investigate how T cell activation affects the estab-lishment of HIV latency. We show that HIV latency can arise from the direct infection of both resting and activated CD4+ T cells. Importantly, returning productively infected cells to a resting state is not associated with a significant silencing of the integrated HIV. We further show that resting CD4+ T cells from human lymphoid tissue (tonsil, spleen) show increased latency after infection when compared to peripheral blood. Our findings raise significant questions regarding the most commonly accepted model for the establishment of latent HIV and suggest that infection of both resting and activated primary CD4+ T cells produce latency. The study of HIV latency has been hindered because there are few latently infected cells in vivo, and we cannot distinguish latently infected cells from uninfected cells prior to reactivation of the latent provirus. In general, HIV latency is quantitatively studied by reactivating latently infected cells after latency has been established. However, this practice limits the investigation of how latency is established and how latent provirus can be reactivated. Our recently developed dual reporter virus, HIV Duo-Fluo I, can identify latently infected cells early after infection. In this study, we use HIV Duo-Fluo I to investigate how T cell activation affects the outcome of HIV infection.
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影响因子：
3.3
作者：
Bonczkowski P;De Spiegelaere W;Bosque A;White CH;Van Nuffel A;Malatinkova E;Kiselinova M;Trypsteen W;Witkowski W;Vermeire J;Verhasselt B;Martins L;Woelk CH;Planelles V;Vandekerckhove L
通讯作者：
Vandekerckhove L
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
56.9
作者：
BUKRINSKY, MI;STANWICK, TL;STEVENSON, M
通讯作者：
STEVENSON, M
DOI：
10.1073/pnas.94.24.13193
发表时间：
1997-11-25
影响因子：
11.1
作者：
Chun, TW;Stuyver, L;Fauci, AS
通讯作者：
Fauci, AS
影响因子：
158.5
作者：
Gulick, RM;Mellors, JW;Chodakewitz, JA
通讯作者：
Chodakewitz, JA