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Cellular Reservoirs of HIV-1 and their Role in Viral Persistence

机译：HIV-1细胞贮库及其在病毒持久性中的作用

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摘要

A major obstacle in human immunodeficiency virus type 1 (HIV-1) eradication is the ability of the virus to remain latent in a subpopulation of the cells it infects. Latently infected cells can escape the viral immune response and persist for long periods of time, despite the presence of successful highly active antiretroviral therapy (HAART). Given the appropriate stimulus, latently infected cells can reactivate and start producing infectious virions. The susceptibility of these cell populations to HIV-1, their life span, their proliferative capacity, and their ability to periodically produce infectious virus subsequent to alterations in cellular physiology and/or immunologic controls are critical issues which determine the contribution of these cells to viral persistence.Memory CD4+ T cells due to the long life span, which may be several years, and their ability to reactivate upon encounter with their cognate antigen or other stimulation, are considered a critical reservoir for maintenance of latent HIV-1 proviral DNA. Cells of the monocyte-macrophage lineage, which originate in the bone marrow (BM), are of particular importance in HIV-1 persistence due to their ability to cross the blood-brain barrier (BBB) and spread HIV-1 infection in the immunoprivileged central nervous system (CNS). Hematopoietic progenitor cells (HPCs) are also a potential HIV-1 reservoir, as several studies have shown that CD34+ HPCs carrying proviral DNA can be found in vivo in a subpopulation of HIV-1-infected patients. The ability of HPCs to proliferate and potentially generate clonal populations of infected cells of the monocyte-macrophage lineage may be crucial in HIV-1 dissemination. The contribution of these and other cell populations in HIV-1 persistence, as well as the possible strategies to eliminate latently infected cells are critically examined in this review.
机译：根除1型人类免疫缺陷病毒（HIV-1）的主要障碍是病毒保持潜伏在它感染的细胞亚群中的能力。尽管存在成功的高活性抗逆转录病毒疗法（HAART），潜在感染的细胞仍可以逃脱病毒的免疫反应并持续很长时间。在适当的刺激下，潜伏感染的细胞可以重新激活并开始产生感染性病毒粒子。这些细胞群对HIV-1的敏感性，寿命，增殖能力以及在细胞生理学和/或免疫控制改变后定期产生传染性病毒的能力是决定这些细胞对病毒贡献的关键问题。由于寿命长（可能长达数年），记忆CD4 + T细胞及其遇到同源抗原或其他刺激时的活化能力被认为是维持潜在HIV-1前病毒DNA的关键储存库。起源于骨髓（BM）的单核巨噬细胞谱系细胞在HIV-1持久性中特别重要，因为它们能够穿过血脑屏障（BBB）并在免疫弱势人群中传播HIV-1感染中枢神经系统（CNS）。造血祖细胞（HPC）也是潜在的HIV-1储库，因为多项研究表明，在感染HIV-1的患者亚群中可以在体内发现带有前病毒DNA的CD34 + HPC。 HPC能够增殖并潜在地产生单核巨噬细胞谱系感染细胞的克隆种群的能力在HIV-1传播中可能至关重要。本文对这些和其他细胞群体在HIV-1持久性中的贡献以及消除潜伏感染细胞的可能策略进行了严格审查。

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