Department of Medicine, Johns Hopkins University School of Medicine, Howard Hughes Medical Institute, Baltimore, Maryland 21205, USA.
Cold Spring Harb Perspect Med. 2011 Sep;1(1):a007096. doi: 10.1101/cshperspect.a007096.
HIV-1 can establish a state of latent infection at the level of individual T cells. Latently infected cells are rare in vivo and appear to arise when activated CD4(+) T cells, the major targets cells for HIV-1, become infected and survive long enough to revert back to a resting memory state, which is nonpermissive for viral gene expression. Because latent virus resides in memory T cells, it persists indefinitely even in patients on potent antiretroviral therapy. This latent reservoir is recognized as a major barrier to curing HIV-1 infection. The molecular mechanisms of latency are complex and include the absence in resting CD4(+) T cells of nuclear forms of key host transcription factors (e.g., NFκB and NFAT), the absence of Tat and associated host factors that promote efficient transcriptional elongation, epigenetic changes inhibiting HIV-1 gene expression, and transcriptional interference. The presence of a latent reservoir for HIV-1 helps explain the presence of very low levels of viremia in patients on antiretroviral therapy. These viruses are released from latently infected cells that have become activated and perhaps from other stable reservoirs but are blocked from additional rounds of replication by the drugs. Several approaches are under exploration for reactivating latent virus with the hope that this will allow elimination of the latent reservoir.
HIV-1 可以在个体 T 细胞水平上建立潜伏感染状态。潜伏感染的细胞在体内很少见，似乎是在 HIV-1 的主要靶细胞——被激活的 CD4(+)T 细胞被感染并存活足够长的时间，恢复到静止的记忆状态时出现的，而这种记忆状态不利于病毒基因表达。由于潜伏病毒存在于记忆 T 细胞中，即使在接受高效抗逆转录病毒治疗的患者中，它也会无限期地持续存在。这种潜伏的病毒库被认为是治愈 HIV-1 感染的主要障碍。潜伏的分子机制很复杂，包括静止的 CD4(+)T 细胞中缺乏关键的宿主转录因子（如 NFκB 和 NFAT）的核形式，缺乏 Tat 和促进有效转录延伸的相关宿主因子，抑制 HIV-1 基因表达的表观遗传变化，以及转录干扰。HIV-1 潜伏库的存在有助于解释接受抗逆转录病毒治疗的患者中极低水平病毒血症的存在。这些病毒是从已被激活的潜伏感染细胞以及其他稳定的病毒库中释放出来的，但被药物阻断了进一步复制的机会。目前正在探索几种激活潜伏病毒的方法，希望这将有助于消除潜伏病毒库。
