生物
表观遗传学
转录因子
转录组
细胞毒性T细胞
病毒潜伏期
Jurkat细胞
细胞生物学
T细胞
病毒学
免疫学
病毒复制
遗传学
细胞培养
基因表达
免疫系统
基因
体外
作者
Yulong Wei,Timothy C. Davenport,Jack A. Collora,Haocong Katherine,Delia Pinto-Santini,Javier R. Lama,Ricardo Alfaro,Ann Duerr,Ya-Chi Ho
出处
期刊:Immunity
[Elsevier]
日期:2023-11-01
卷期号:56 (11): 2584-2601.e7
被引量:3
标识
DOI:10.1016/j.immuni.2023.10.002
摘要
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 factor accessibility, transcriptome, surface proteins, HIV-1 DNA, and HIV-1 RNA in memory CD4+ T cells from six people living with HIV-1 during viremia and after suppressive antiretroviral therapy. We identified increased transcription factor accessibility in latent HIV-1-infected cells (RORC) and transcriptionally active HIV-1-infected cells (interferon regulatory transcription 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 cellular states 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 and cellular programs promoting HIV-1 persistence.
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