Histone chaperone CAF‐1 promotes HIV‐1 latency by leading the formation of phase‐separated suppressive nuclear bodies |
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Authors: | Xiancai Ma Tao Chen Zhilin Peng Ziwen Wang Jun Liu Tao Yang Liyang Wu Guangyan Liu Mo Zhou Muye Tong Yuanjun Guan Xu Zhang Yingtong Lin Xiaoping Tang Linghua Li Zhonghui Tang Ting Pan Hui Zhang |
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Abstract: | 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. |
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Keywords: | CAF‐ 1, epigenetic regulation, HIV‐ 1 latency, nuclear body, phase separation |
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