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CAF-1 promotes HIV-1 latency by leading the formation of phase-separated suppressive nuclear bodies.

ABSTRACT: HIV-1 latency is a major obstacle to achieve a functional cure for AIDS. To eradicate the viral reservoir, one of the strategies is to specifically reactivate HIV-1-infected cells and followed by elimination with potent immune surveillance. However, present latency-reversing agents (LRAs) are quite dissatisfactory because of their high toxicity and low efficiency. New targets need to be identified to develop more promising LRAs. Here, we found that histone chaperone chromatin assembly factor 1 (CAF-1) promotes HIV-1 latency by forming versatile suppressive nuclear bodies. CAF-1 plays a leading role for the formation of bodies recruiting multi-layer suppressive epigenetic modifiers and maintainers, and is of the characteristic of liquid-liquid phase separation (LLPS). Three distinct disordered regions of CHAF1A subunit coalesce CAF-1 body components by forming LLPS and play a key in maintaining HIV-1 latency. Therefore, disruptive induction of phase-separated CAF-1 body could be an important strategy to reactivate latent HIV-1.

ORGANISM(S): Homo sapiens

PROVIDER: GSE166337 | GEO | 2021/02/09

REPOSITORIES: GEO

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CAF-1 promotes HIV-1 latency by leading the formation of phase-separated suppressive nuclear bodies

Project description:HIV-1 latency is a major obstacle to achieve a functional cure for AIDS. To eradicate the viral reservoir, one of the strategies is to specifically reactivate HIV-1-infected cells and followed by elimination with potent immune surveillance. However, present latency-reversing agents (LRAs) are quite dissatisfactory because of their high toxicity and low efficiency. New targets need to be identified to develop more promising LRAs. Here, we found that histone chaperone chromatin assembly factor 1 (CAF-1) promotes HIV-1 latency by forming versatile suppressive nuclear bodies. CAF-1 plays a leading role for the formation of bodies recruiting multi-layer suppressive epigenetic modifiers and maintainers, and is of the characteristic of liquid-liquid phase separation (LLPS). Three distinct disordered regions of CHAF1A subunit coalesce CAF-1 body components by forming LLPS and play a key in maintaining HIV-1 latency. Therefore, disruptive induction of phase-separated CAF-1 body could be an important strategy to reactivate latent HIV-1.

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CAF-1 promotes HIV-1 latency by leading the formation of phase-separated suppressive nuclear bodies.

Project description:CAF-1 promotes HIV-1 latency by leading the formation of phase-separated suppressive nuclear bodies.

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