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人类免疫缺陷病毒(HIV)感染的前病毒储存库

The Proviral Reservoirs of Human Immunodeficiency Virus (HIV) Infection.

作者信息

Murzin Andrey I, Elfimov Kirill A, Gashnikova Natalia M

机构信息

State Research Center of Virology and Biotechnology "Vector", Koltsovo 630559, Russia.

出版信息

Pathogens. 2024 Dec 30;14(1):15. doi: 10.3390/pathogens14010015.

Abstract

Human Immunodeficiency Virus (HIV) proviral reservoirs are cells that harbor integrated HIV proviral DNA within their nuclear genomes. These cells form a heterogeneous group, represented by peripheral blood mononuclear cells (PBMCs), tissue-resident lymphoid and monocytic cells, and glial cells of the central nervous system. The importance of studying the properties of proviral reservoirs is connected with the inaccessibility of integrated HIV proviral DNA for modern anti-retroviral therapies (ARTs) that block virus reproduction. If treatment is not effective enough or is interrupted, the proviral reservoir can reactivate. Early initiation of ART improves the prognosis of the course of HIV infection, which is explained by the reduction in the proviral reservoir pool observed in the early stages of the disease. Different HIV subtypes present differences in the number of latent reservoirs, as determined by structural and functional differences. Unique signatures of patients with HIV, such as elite controllers, have control over viral replication and can be said to have achieved a functional cure for HIV infection. Uncovering the causes of this phenomenon will bring humanity closer to curing HIV infection, potential approaches to which include stem cell transplantation, clustered regularly interspaced short palindromic repeats (CRISPR)/cas9, "Shock and kill", "Block and lock", and the application of broad-spectrum neutralizing antibodies (bNAbs).

摘要

人类免疫缺陷病毒(HIV)前病毒储存库是指在其核基因组中含有整合型HIV前病毒DNA的细胞。这些细胞构成了一个异质性群体,以外周血单核细胞(PBMC)、组织驻留淋巴细胞和单核细胞以及中枢神经系统的神经胶质细胞为代表。研究前病毒储存库特性的重要性与现代抗逆转录病毒疗法(ART)无法触及整合型HIV前病毒DNA有关,而抗逆转录病毒疗法会阻断病毒复制。如果治疗效果不够好或中断,前病毒储存库可能会重新激活。早期启动抗逆转录病毒疗法可改善HIV感染病程的预后,这可以通过在疾病早期观察到的前病毒储存库数量减少来解释。不同的HIV亚型在潜伏储存库数量上存在差异,这是由结构和功能差异决定的。HIV患者的独特特征,如精英控制者,能够控制病毒复制,可以说已实现了对HIV感染的功能性治愈。揭示这一现象的原因将使人类更接近治愈HIV感染,潜在的方法包括干细胞移植、成簇规律间隔短回文重复序列(CRISPR)/cas9、“激活并杀死”、“阻断并锁定”以及应用广谱中和抗体(bNAb)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fb/11768375/28bd6b56fdc3/pathogens-14-00015-g001.jpg

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