HIV-1 Latency and Eradication: Past, Present and Future.
HIV-1 Latency and Eradication: Past, Present and Future.
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DOI：
10.2174/1570162x14666160324125536
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发表时间：
2016
影响因子：
1
通讯作者：
Khalili K
中科院分区：
文献类型：
--
作者：
Datta PK;Kaminski R;Hu W;Pirrone V;Sullivan NT;Nonnemacher MR;Dampier W;Wigdahl B;Khalili K
众所周知，抗逆转录病毒疗法（ART）虽然在控制艾滋病毒复制方面非常有效，但不能从体内消除病毒。因此，由于受感染的储库细胞作为病毒重新出现的来源而持续存在，大多数hiv -1感染者仍然有发展为艾滋病的风险。已经确定了几个包含复制能力HIV-1的储存库，最显著的是CD4+ T细胞。髓系细胞是抵抗病原体的第一道防线，参与HIV向庇护器官的传播，同时也是HIV-1的细胞储存库。在潜伏感染的静止CD4+ T细胞中，原病毒DNA的整合拷贝保持休眠状态，但在细胞激活后具有产生复制能力的病毒的能力。研究表明，染色质结构的修饰在持久性的建立中起作用，这在一定程度上表明潜伏期是由表观遗传控制的。目前从这些细胞群中根除HIV-1的努力主要集中在“休克和杀伤”方法上，通过细胞再激活来触发细胞溶解或宿主免疫反应来消除产生病毒的细胞。然而，研究揭示了这种方法的一些局限性，需要更多的研究来评估其临床应用。基因编辑技术的最新进展促使人们使用这种方法来灭活潜伏感染细胞基因组中的整合前病毒DNA。这项技术需要对病毒遗传学的详细了解和强大的传递能力，可以作为消除宿主潜伏库的有力策略，从而实现艾滋病的无菌治疗。
It is well established that antiretroviral therapy (ART), while highly effective in controlling HIV replication, cannot eliminate virus from the body. Therefore, the majority of HIV-1-infected individuals remain at risk for developing AIDS due to persistence of infected reservoir cells serving as a source of virus re-emergence. Several reservoirs containing replication competent HIV-1 have been identified, most notably CD4+ T cells. Cells of the myeloid lineage, which are the first line of defense against pathogens and participate in HIV dissemination into sanctuary organs, also serve as cellular reservoirs of HIV-1. In latently infected resting CD4+ T cells, the integrated copies of proviral DNA remain in a dormant state, yet possess the ability to produce replication competent virus after cellular activation. Studies have demonstrated that modification of chromatin structure plays a role in establishing persistence, in part suggesting that latency is, controlled epigenetically. Current efforts to eradicate HIV-1 from this cell population focus primarily on a “shock and kill” approach through cellular reactivation to trigger elimination of virus producing cells by cytolysis or host immune responses. However, studies revealed several limitations to this approach that require more investigation to assess its clinical application. Recent advances in gene editing technology prompted use of this approach for inactivating integrated proviral DNA in the genome of latently infected cells. This technology, which requires a detailed understanding of the viral genetics and robust delivery, may serve as a powerful strategy to eliminate the latent reservoir in the host leading to a sterile cure of AIDS.
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