HIV-1 Latency and Viral Reservoirs: Existing Reversal Approaches and Potential Technologies, Targets, and Pathways Involved in HIV Latency Studies.
HIV-1 Latency and Viral Reservoirs: Existing Reversal Approaches and Potential Technologies, Targets, and Pathways Involved in HIV Latency Studies.
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HIV-1潜伏期和病毒库：现有的抑制方法和潜在的技术，目标和途径参与HIV潜伏期研究。
作者：
Khanal S;Schank M;El Gazzar M;Moorman JP;Yao ZQ
根除潜伏的人类免疫缺陷病毒（艾滋病毒）感染是一项全球性的健康挑战。重新激活HIV潜伏期和杀死病毒感染的细胞，即所谓的“踢和杀”或“休克和杀”方法，是治疗HIV的流行策略。虽然抗逆转录病毒疗法（ART）通过靶向HIV生命周期中的多个步骤（包括病毒进入、整合、复制和生产）来阻止HIV复制，但它无法摆脱并入宿主细胞基因组中的隐匿性前病毒。这些潜伏的前病毒具有复制能力，在ART中断或停止的情况下可以反弹。一般来说，一个非常小的细胞群体携带前病毒，作为ART控制的HIV受试者的储存库，并且能够表达很少或不表达HIV RNA或蛋白质。除了典型的静息记忆CD 4 + T细胞外，HIV储库还存在于组织巨噬细胞、骨髓细胞、脑小胶质细胞、肠上皮细胞和造血干细胞（HSC）中。尽管缺乏活跃的病毒产生，潜伏性HIV感染的受试者继续表现出异常的细胞信号传导和代谢功能障碍，导致轻微至严重的细胞和全身并发症或合并症。这些包括基因组DNA损伤;端粒磨损;线粒体功能障碍;过早衰老;以及淋巴细胞、心脏、肾脏、肝脏或肺功能障碍。因此，涉及HIV潜伏期及其逆转的《双城之战》机制需要进一步研究，以确定HIV储库形成和清除的神秘机制。在这篇综述中，我们讨论了几种分子和信号通路，其中一些在维持或逆转HIV潜伏期和水库中具有双重作用，并描述了一些不断发展的策略和可能的方法，以消除病毒水库，并最终治愈/根除HIV感染。
Eradication of latent human immunodeficiency virus (HIV) infection is a global health challenge. Reactivation of HIV latency and killing of virus-infected cells, the so-called “kick and kill” or “shock and kill” approaches, are a popular strategy for HIV cure. While antiretroviral therapy (ART) halts HIV replication by targeting multiple steps in the HIV life cycle, including viral entry, integration, replication, and production, it cannot get rid of the occult provirus incorporated into the host-cell genome. These latent proviruses are replication-competent and can rebound in cases of ART interruption or cessation. In general, a very small population of cells harbor provirus, serve as reservoirs in ART-controlled HIV subjects, and are capable of expressing little to no HIV RNA or proteins. Beyond the canonical resting memory CD4+ T cells, HIV reservoirs also exist within tissue macrophages, myeloid cells, brain microglial cells, gut epithelial cells, and hematopoietic stem cells (HSCs). Despite a lack of active viral production, latently HIV-infected subjects continue to exhibit aberrant cellular signaling and metabolic dysfunction, leading to minor to major cellular and systemic complications or comorbidities. These include genomic DNA damage; telomere attrition; mitochondrial dysfunction; premature aging; and lymphocytic, cardiac, renal, hepatic, or pulmonary dysfunctions. Therefore, the arcane machineries involved in HIV latency and its reversal warrant further studies to identify the cryptic mechanisms of HIV reservoir formation and clearance. In this review, we discuss several molecules and signaling pathways, some of which have dual roles in maintaining or reversing HIV latency and reservoirs, and describe some evolving strategies and possible approaches to eliminate viral reservoirs and, ultimately, cure/eradicate HIV infection.
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影响因子：
8.8
作者：
Bosque A;Nilson KA;Macedo AB;Spivak AM;Archin NM;Van Wagoner RM;Martins LJ;Novis CL;Szaniawski MA;Ireland CM;Margolis DM;Price DH;Planelles V
通讯作者：
Planelles V
影响因子：
4.8
作者：
Barclay, Robert A.;Schwab, Angela;Kashanchi, Fatah
通讯作者：
Kashanchi, Fatah
影响因子：
6.4
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Campbell, Grant R.;To, Rachel K.;Spector, Stephen A.
通讯作者：
Spector, Stephen A.
影响因子：
20.3
作者：
Bosque, Alberto;Planelles, Vicente
通讯作者：
Planelles, Vicente
影响因子：
3.7
作者：
Bobardt, Michael;Kuo, Joseph;Gallay, Philippe A.
通讯作者：
Gallay, Philippe A.