Proliferation of HIV-1 reservoir cells: The delusion of infinite growth.
Proliferation of HIV-1 reservoir cells: The delusion of infinite growth.
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HIV-1 储存细胞的增殖：无限生长的错觉。
DOI：
10.1084/jem.20232321
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Lichterfeld,Mathias
中科院分区：
文献类型：
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作者：
Lancien,Melanie;Lichterfeld,Mathias
尽管进行了抗逆转录病毒治疗，HIV-1 感染细胞的增殖仍会导致病毒持续存在。 Kufera 等人的一项新研究 (https://doi.org/10.1084/jem.20231511) 表明，感染基因组完整的 HIV-1 的细胞的增殖生长并非无限；相反，这些细胞似乎至少对 TCR 刺激有部分抵抗力，从而限制了它们响应抗原挑战而增殖的能力。 尽管 HIV-1 在 40 多年前首次被发现，但它在很大程度上仍然是“我们这个时代的流行病”，全世界约有 3,900 万 HIV-1 感染者，没有可用的治疗方法；终身抗逆转录病毒抑制治疗是所有 HIV-1 感染者唯一可用的治疗选择。尽管进行了抗逆转录病毒治疗，HIV-1 仍持续存在，这是由于少量病毒感染的 CD4 T 细胞携带染色体整合的、基因组完整的病毒 DNA，一旦治疗中断，这些病毒 DNA 会导致病毒反弹（Finzi 等，1997）。最近，在理解这些所谓的“病毒储存细胞”长期存活的机制方面已经取得了相当大的进展：通过感染 CD4 T 细胞（这些细胞旨在长期存在以提供持续的细胞免疫记忆），HIV-1 劫持了本质上高度耐用且能够响应抗原刺激或细胞因子信号而增殖的细胞群。受感染细胞的这种增殖能力似乎代表了支持 HIV-1 持续存在的主要机制之一。事实上，用单基因组近全长测序对受感染细胞进行分子分析经常揭示出含有相同原病毒序列和相应染色体整合位点的大细胞簇，
Proliferation of HIV-1–infected cells contributes to viral persistence despite antiretroviral therapy. A new study by Kufera et al.(https://doi. org/10.1084/jem. 20231511) demonstrates that proliferative growth of cells infected with genome-intact HIV-1 is not limitless; rather, these cells seem to be at least partially refractory to TCR stimulation, restricting their ability to proliferate in response to antigenic challenge.Although HIV-1 was first discovered more than 40 years ago, it largely remains the “epidemic of our time,” with∼ 39 million people living with HIV-1 worldwide for whom no curative treatment approaches are available; lifelong antiretroviral suppression treatment represents the only available therapeutic option for all people living with HIV-1. Persistence of HIV-1 despite antiretroviral treatment is due to small numbers of virally infected CD4 T cells harboring chromosomally integrated, genome-intact viral DNA that can drive viral rebound once treatment is interrupted (Finzi et al., 1997). Considerable progress has been made recently in understanding the mechanisms that permit long-term survival of these socalled “viral reservoir cells”: By infecting CD4 T cells, which are designed to persist long-term to provide sustained cellular immune memory, HIV-1 hijacks a cell population that is intrinsically highly durable and able to proliferate in response to antigenic stimulation or cytokine signals. This proliferative ability of infected cells seems to represent one of the principal mechanisms supporting HIV-1 persistence. Indeed, molecular profiling of infected cells with single-genome near full-length sequencing frequently revealed large clusters of cells that contain identical proviral sequences and corresponding chromosomal integration sites,