Targeting HIV persistence in the tissue.

Current opinion in HIV and AIDS Pub Date : 2024-03-01 Epub Date: 2024-01-08 DOI:10.1097/COH.0000000000000836
Daan K J Pieren, Aleix Benítez-Martínez, Meritxell Genescà
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Abstract

Purpose of review: The complex nature and distribution of the HIV reservoir in tissue of people with HIV remains one of the major obstacles to achieve the elimination of HIV persistence. Challenges include the tissue-specific states of latency and viral persistence, which translates into high levels of reservoir heterogeneity. Moreover, the best strategies to reach and eliminate these reservoirs may differ based on the intrinsic characteristics of the cellular and anatomical reservoir to reach.

Recent findings: While major focus has been undertaken for lymphoid tissues and follicular T helper cells, evidence of viral persistence in HIV and non-HIV antigen-specific CD4 + T cells and macrophages resident in multiple tissues providing long-term protection presents new challenges in the quest for an HIV cure. Considering the microenvironments where these cellular reservoirs persist opens new venues for the delivery of drugs and immunotherapies to target these niches. New tools, such as single-cell RNA sequencing, CRISPR screenings, mRNA technology or tissue organoids are quickly developing and providing detailed information about the complex nature of the tissue reservoirs.

Summary: Targeting persistence in tissue reservoirs represents a complex but essential step towards achieving HIV cure. Combinatorial strategies, particularly during the early phases of infection to impact initial reservoirs, capable of reaching and reactivating multiple long-lived reservoirs in the body may lead the path.

针对艾滋病病毒在组织中的持续存在。
审查的目的:艾滋病病毒感染者组织中艾滋病病毒储库的性质和分布十分复杂,这仍然是消除艾滋病病毒持续存在的主要障碍之一。面临的挑战包括潜伏期和病毒持续存在的组织特异性状态,这意味着储库的高度异质性。此外,根据细胞和解剖储库的固有特征,达到和消除这些储库的最佳策略也可能不同:最近的研究结果:虽然研究的主要重点是淋巴组织和滤泡 T 辅助细胞,但有证据表明,艾滋病毒和非艾滋病毒抗原特异性 CD4+ T 细胞以及驻留在多种组织中提供长期保护的巨噬细胞中的病毒持续存在,这为寻求治愈艾滋病毒的方法提出了新的挑战。考虑到这些细胞库持续存在的微环境,为针对这些龛位提供药物和免疫疗法开辟了新的途径。单细胞 RNA 测序、CRISPR 筛选、mRNA 技术或组织器官模型等新工具正在迅速发展,并提供了有关组织储库复杂性质的详细信息。组合策略,尤其是在感染早期阶段影响初始储库,能够到达并重新激活体内多个长效储库,可能会引领这条道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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