National Center for Biodefense and Infectious Disease, George Mason University, Manassas, Virginia 20109, United States of America.
Mol Med. 2012 Sep 25;18(1):1096-108. doi: 10.2119/molmed.2012.00194.
Failure of highly active antiretroviral therapy to eradicate the human immunodeficiency virus (HIV), even in patients who suppress the virus to undetectable levels for many years, underscores the problems associated with fighting this infection. The existence of persistent infection in certain cellular and anatomical reservoirs appears to be the major hurdle in HIV eradication. The development of therapeutic interventions that eliminate or limit the latent viral pools or prevent the reemergence of the viruses from producing cells will therefore be required to enhance the effectiveness of current antiretroviral strategies. To achieve this goal, there is a pressing need to understand HIV latency at the molecular level to design novel and improved therapies to either eradicate HIV or find a functional cure in which patients could maintain a manageable viral pool without AIDS in the absence of antiretroviral therapy. The integrated proviral genome remains transcriptionally silent for a long period in certain subsets of T cells. This ability to infect cells latently helps HIV to establish a persistent infection despite strong humoral and cellular immune responses against the viral proteins. The main purpose of this report is to provide a general overview of the HIV latency. We will describe the hurdles being faced in eradicating latent HIV proviruses. We will also briefly discuss the ongoing strategies aimed toward curing HIV infection.
高效抗逆转录病毒疗法未能根除人类免疫缺陷病毒（HIV），即使在抑制病毒多年达到无法检测水平的患者中也是如此，这凸显了与这种感染作斗争所面临的问题。在某些细胞和解剖学储库中持续存在感染，似乎是 HIV 根除的主要障碍。因此，需要开发消除或限制潜伏病毒库的治疗干预措施，或防止病毒从产生细胞重新出现，以增强当前抗逆转录病毒策略的有效性。为了实现这一目标，迫切需要从分子水平了解 HIV 潜伏期，以设计新型和改进的疗法，要么根除 HIV，要么找到功能性治愈，使患者在没有抗逆转录病毒治疗的情况下，能够维持可管理的病毒库而不发生艾滋病。在某些 T 细胞亚群中，整合的前病毒基因组在很长一段时间内保持转录沉默。这种潜伏感染细胞的能力有助于 HIV 建立持续性感染，尽管针对病毒蛋白存在强烈的体液和细胞免疫反应。本报告的主要目的是提供 HIV 潜伏期的概述。我们将描述在根除潜伏 HIV 前病毒方面面临的障碍。我们还将简要讨论旨在治愈 HIV 感染的正在进行的策略。
