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Histone chaperone CAF‐1 promotes HIV‐1 latency by leading the formation of phase‐separated suppressive nuclear bodies
Author(s) -
Ma Xiancai,
Chen Tao,
Peng Zhilin,
Wang Ziwen,
Liu Jun,
Yang Tao,
Wu Liyang,
Liu Guangyan,
Zhou Mo,
Tong Muye,
Guan Yuanjun,
Zhang Xu,
Lin Yingtong,
Tang Xiaoping,
Li Linghua,
Tang Zhonghui,
Pan Ting,
Zhang Hui
Publication year - 2021
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020106632
Subject(s) - christian ministry , china , library science , medicine , geography , family medicine , political science , law , archaeology , computer science
HIV‐1 latency is a major obstacle to achieving a functional cure for AIDS. Reactivation of HIV‐1‐infected cells followed by their elimination via immune surveillance is one proposed strategy for eradicating the viral reservoir. However, current latency‐reversing agents (LRAs) show high toxicity and low efficiency, and new targets are needed to develop more promising LRAs. Here, we found that the histone chaperone CAF‐1 (chromatin assembly factor 1) is enriched on the HIV‐1 long terminal repeat (LTR) and forms nuclear bodies with liquid–liquid phase separation (LLPS) properties. CAF‐1 recruits epigenetic modifiers and histone chaperones to the nuclear bodies to establish and maintain HIV‐1 latency in different latency models and primary CD4 + T cells. Three disordered regions of the CHAF1A subunit are important for phase‐separated CAF‐1 nuclear body formation and play a key role in maintaining HIV‐1 latency. Disruption of phase‐separated CAF‐1 bodies could be a potential strategy to reactivate latent HIV‐1.