PEBP1 suppresses HIV transcription and induces latency by inactivating MAPK/NF-?B signaling

ABSTRACT: The latent HIV-1 reservoir is a major barrier to viral eradication. However, our understanding of how HIV-1 establishes latency is incomplete. Here, by performing a genome-wide CRISPR-Cas9 knockout library screen, we identify Phosphatidylethanolamine-binding protein 1 (PEBP1), also known as Raf kinase inhibitor protein (RKIP), as a novel gene inducing HIV latency. Depletion of PEBP1 leads to the reactivation of HIV-1 in multiple models of latency. Mechanistically, PEBP1 de-phosphorylates Raf1/ERK/I?B and IKK/I?B signaling pathways to sequestrate NF-?B in the cytoplasm, which transcriptionally inactivates HIV-1 to induce latency. Importantly, the induction of PEBP1 expression by the green tea compound epigallocatechin-3-gallate (EGCG), prevents latency reversal by inhibiting nuclear translo

SUBMITTER: Mr. Xinyi Yang 

PROVIDER: S-SCDT-EMBOR-2019-49305V1 | biostudies-other |

REPOSITORIES: biostudies-other