Journal
EMBO JOURNAL
Volume 40, Issue 10, Pages -Publisher
WILEY
DOI: 10.15252/embj.2020106632
Keywords
CAF‐ 1; epigenetic regulation; HIV‐ 1 latency; nuclear body; phase separation
Categories
Funding
- National Special Research Program of China for Important Infectious Diseases [2018ZX10302103, 2017ZX10202102]
- Important Key Program of Natural Science Foundation of China [81730060]
- Joint-innovation Program in Healthcare for Special Scientific Research Projects of Guangzhou [201803040002]
- National Postdoctoral Program for Innovative Talents
- General Program of China Postdoctoral Science Foundation [BX20190398, 2019M663215]
- National Natural Science Foundation of China [81702856]
- Pearl River S&T Nova Program of Guangzhou [201806010118]
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HIV-1 latency is a major challenge in achieving a functional cure for AIDS, and the histone chaperone CAF-1 plays a crucial role in maintaining this latency. Disruption of phase-separated CAF-1 bodies could be a potential strategy for reactivating latent HIV-1.
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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