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PEBP 1 suppresses HIV transcription and induces latency by inactivating MAPK / NF ‐κB signaling
Author(s) -
Yang Xinyi,
Wang Yanan,
Lu Panpan,
Shen Yinzhong,
Zhao Xiaying,
Zhu Yuqi,
Jiang Zhengtao,
Yang He,
Pan Hanyu,
Zhao Lin,
Zhong Yangcheng,
Wang Jing,
Liang Zhiming,
Shen Xiaoting,
Lu Daru,
Jiang Shibo,
Xu Jianqing,
Wu Hao,
Lu Hongzhou,
Jiang Guochun,
Zhu Huanzhang
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201949305
Subject(s) - biology , microbiology and biotechnology , mapk/erk pathway , nf κb , virus latency , kinase , signal transduction , transcription factor , transcription (linguistics) , immunology , gene , biochemistry , virus , viral replication , linguistics , philosophy
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 ( PEBP 1), also known as Raf kinase inhibitor protein ( RKIP ), as a novel gene inducing HIV latency. Depletion of PEBP 1 leads to the reactivation of HIV ‐1 in multiple models of latency. Mechanistically, PEBP 1 de‐phosphorylates Raf1/ ERK /IκB and IKK /IκB signaling pathways to sequestrate NF ‐κB in the cytoplasm, which transcriptionally inactivates HIV ‐1 to induce latency. Importantly, the induction of PEBP 1 expression by the green tea compound epigallocatechin‐3‐gallate ( EGCG ) prevents latency reversal by inhibiting nuclear translocation of NF ‐κB, thereby suppressing HIV ‐1 transcription in primary CD4 + T cells isolated from patients receiving antiretroviral therapy ( ART ). These results suggest a critical role for PEBP 1 in the regulation of upstream NF ‐κB signaling pathways governing HIV transcription. Targeting of this pathway could be an option to control HIV reservoirs in patients in the future.