美国耶鲁大学医学院Ya-Chi Ho团队近期取得重要工作进展。他们研究提出潜伏和活性HIV-1库的单细胞表观遗传学、转录和蛋白质谱分析显示IKZF3促进HIV-1的持久性。相关研究成果2023年11月2日在线发表于《免疫》杂志上。

据介绍，认识HIV-1感染的细胞如何增殖和持续是根除HIV-1的关键，但HIV-1感染细胞的异质性和稀有性阻碍了机制的探究。

研究人员使用单细胞DOGMA-seq在病毒血症期间和抑制性抗逆转录病毒治疗后，从6名HIV-1患者的记忆CD4⁺ T细胞中同时捕获转录因子可及性、转录组、表面蛋白、HIV-1 DNA和HIV-1 RNA。研究人员在潜伏性HIV-1感染细胞（RORC）和转录活性HIV-1感染的细胞（干扰素调节转录因子[IRF]和激活蛋白1[AP-1]）中发现了转录因子可及性的增加。增殖程序（IKZF3、IL21、BIRC5和MKI67共表达）促进了转录活性HIV-1感染细胞的存活。潜伏性和转录活性HIV-1感染的细胞都增加了IKZF3（Aiolos）的表达。不同的表观遗传学程序驱动了HIV-1感染细胞的异质性细胞状态（IRF：激活，Eomes：细胞毒性效应器分化，AP-1：迁移和细胞死亡）。

总之，这一研究揭示了潜伏和转录活性HIV-1感染细胞的单细胞表观遗传学、转录和蛋白质状态，以及促进HIV-1持久性的细胞程序。

附：英文原文

Title: Single-cell epigenetic, transcriptional, and protein profiling of latent and active HIV-1 reservoir revealed that IKZF3 promotes HIV-1 persistence

Author: Yulong Wei, Timothy C. Davenport, Jack A. Collora, Haocong Katherine Ma, Delia Pinto-Santini, Javier Lama, Ricardo Alfaro, Ann Duerr, Ya-Chi Ho

Issue&Volume: 2023-11-02

Abstract: Understanding how HIV-1-infected cells proliferate and persist is key to HIV-1 eradication,but the heterogeneity and rarity of HIV-1-infected cells hamper mechanistic interrogations.Here, we used single-cell DOGMA-seq to simultaneously capture transcription factoraccessibility, transcriptome, surface proteins, HIV-1 DNA, and HIV-1 RNA in memoryCD4+ T cells from six people living with HIV-1 during viremia and after suppressive antiretroviraltherapy. We identified increased transcription factor accessibility in latent HIV-1-infectedcells (RORC) and transcriptionally active HIV-1-infected cells (interferon regulatorytranscription factor [IRF] and activator protein 1 [AP-1]). A proliferation program(IKZF3, IL21, BIRC5, and MKI67 co-expression) promoted the survival of transcriptionally active HIV-1-infected cells.Both latent and transcriptionally active HIV-1-infected cells had increased IKZF3 (Aiolos) expression. Distinct epigenetic programs drove the heterogeneous cellularstates of HIV-1-infected cells: IRF:activation, Eomes:cytotoxic effector differentiation,AP-1:migration, and cell death. Our study revealed the single-cell epigenetic, transcriptional,and protein states of latent and transcriptionally active HIV-1-infected cells andcellular programs promoting HIV-1 persistence.

DOI: 10.1016/j.immuni.2023.10.002

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00442-9