无药物控制 HIV-1 感染者的 "阻断和锁定 "病毒整合位点。

Current opinion in HIV and AIDS Pub Date : 2024-05-01 Epub Date: 2024-02-28 DOI:10.1097/COH.0000000000000845
Benjamin Bone, Mathias Lichterfeld
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引用次数: 0

摘要

综述的目的:精英控制者(ECs)和治疗后控制者(PTCs)代表了一小部分个体,他们能够在不使用药物的情况下维持对 HIV 血浆病毒载量的控制,尽管有一个具有复制能力的病毒库持续存在。本综述旨在整理近期对病毒库进行评估的实验研究,这些病毒库能够区分EC/PTC,并可能有助于他们在没有抗逆转录病毒疗法的情况下维持检测不到的病毒载量:最近对EC的研究表明,EC/PTC中完整前病毒的整合位点明显偏向于异染色质区域;相比之下,在可接触染色质和允许染色质中的完整前病毒所占比例极低。值得注意的是,EC的CD4+ T细胞在体外直接感染时并没有发现这种偏倚,这表明EC的病毒库特征与急性感染期间整合位点偏好的改变无关,而是免疫介导的选择机制的结果,这种机制可以消除转录活跃的超染色质区域的前病毒,同时促进完整的前病毒在非允许的基因组区域优先持续存在。这种 "封锁和锁定 "区域中的前病毒转录可能通过表观遗传机制受到限制,从而保护它们不被免疫识别,但可能限制了它们驱动病毒反弹的能力。虽然驱动这一选择过程的确切免疫机制仍未确定,但最近的单细胞分析方法支持这样的假设,即 HIV 储库细胞受到宿主因素的免疫选择压力。摘要:"阻断和锁定 "病毒储库特征可能是功能性治愈 HIV-1 感染的结构性病毒学相关因素。有必要进一步研究促进 EC/PTC 中 HIV-1 储库选择和进化的免疫学机制,并为可预见的治愈策略提供信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
"Block and lock" viral integration sites in persons with drug-free control of HIV-1 infection.

Purpose of review: Elite controllers (ECs) and Posttreatment controllers (PTCs) represent a small subset of individuals who are capable of maintaining drug-free control of HIV plasma viral loads despite the persistence of a replication-competent viral reservoir. This review aims to curate recent experimental studies evaluating viral reservoirs that distinguish EC/PTC and may contribute to their ability to maintain undetectable viral loads in the absence of antiretroviral therapy.

Recent findings: Recent studies on ECs have demonstrated that integration sites of intact proviruses in EC/PTC are markedly biased towards heterochromatin regions; in contrast, intact proviruses in accessible and permissive chromatin were profoundly underrepresented. Of note, no such biases were noted when CD4 + T cells from EC were infected directly ex vivo, suggesting that the viral reservoir profile in EC is not related to altered integration site preferences during acute infection, but instead represents the result of immune-mediated selection mechanisms that can eliminate proviruses in transcriptionally-active euchromatin regions while promoting preferential persistence of intact proviruses in nonpermissive genome regions. Proviral transcription in such "blocked and locked" regions may be restricted through epigenetic mechanisms, protecting them from immune-recognition but presumably limiting their ability to drive viral rebound. While the exact immune mechanisms driving this selection process remain undefined, recent single-cell analytic approaches support the hypothesis that HIV reservoir cells are subject to immune selection pressure by host factors.

Summary: A "blocked and locked" viral reservoir profile may constitute a structural virological correlate of a functional cure of HIV-1 infection. Further research into the immunological mechanism promoting HIV-1 reservoir selection and evolution in EC/PTC is warranted and could inform foreseeable cure strategies.

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