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HIV-1在中枢神经系统中的持续存在:潜伏机制、发病机制及根除策略的最新进展

HIV-1 persistence in the CNS: Mechanisms of latency, pathogenesis and an update on eradication strategies.

作者信息

Sonti Shilpa, Sharma Adhikarimayum Lakhikumar, Tyagi Mudit

机构信息

Center for Translational Medicine, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.

Center for Translational Medicine, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.

出版信息

Virus Res. 2021 Oct 2;303:198523. doi: 10.1016/j.virusres.2021.198523. Epub 2021 Jul 24.

Abstract

Despite four decades of research into the human immunodeficiency virus (HIV-1), a successful strategy to eradicate the virus post-infection is lacking. The major reason for this is the persistence of the virus in certain anatomical reservoirs where it can become latent and remain quiescent for as long as the cellular reservoir is alive. The Central Nervous System (CNS), in particular, is an intriguing anatomical compartment that is tightly regulated by the blood-brain barrier. Targeting the CNS viral reservoir is a major challenge owing to the decreased permeability of drugs into the CNS and the cellular microenvironment that facilitates the compartmentalization and evolution of the virus. Therefore, despite effective antiretroviral (ARV) treatment, virus persists in the CNS, and leads to neurological and neurocognitive deficits. To date, viral eradication strategies fail to eliminate the virus from the CNS. To facilitate the improvement of the existing elimination strategies, as well as the development of potential therapeutic targets, the aim of this review is to provide an in-depth understanding of HIV latency in CNS and the onset of HIV-1 associated neurological disorders.

摘要

尽管对人类免疫缺陷病毒(HIV-1)进行了四十年的研究,但仍缺乏一种在感染后根除该病毒的成功策略。主要原因是病毒在某些解剖学储存库中持续存在,在这些储存库中它可以潜伏,并在细胞储存库存活期间一直保持静止状态。特别是中枢神经系统(CNS),是一个受血脑屏障严格调节的有趣解剖学区域。由于药物进入中枢神经系统的通透性降低以及促进病毒分隔和进化的细胞微环境,靶向中枢神经系统病毒储存库是一项重大挑战。因此,尽管有有效的抗逆转录病毒(ARV)治疗,但病毒仍在中枢神经系统中持续存在,并导致神经和神经认知缺陷。迄今为止,病毒根除策略未能从中枢神经系统中清除病毒。为了促进现有清除策略的改进以及潜在治疗靶点的开发,本综述的目的是深入了解中枢神经系统中的HIV潜伏状态以及HIV-1相关神经疾病的发病机制。

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