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AP‐1 and NF‐κB synergize to transcriptionally activate latent HIV upon T‐cell receptor activation
Author(s) -
Hokello Joseph,
Lakhikumar Sharma Adhikarimayum,
Tyagi Mudit
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14033
Subject(s) - nfat , jurkat cells , lytic cycle , t cell receptor , virus latency , biology , t cell , transcription factor , transcription (linguistics) , co receptor , virology , human immunodeficiency virus (hiv) , microbiology and biotechnology , genetics , viral replication , virus , immune system , gene , linguistics , philosophy
Latent HIV‐1 proviruses are capable of reactivating productive lytic infection, but the precise molecular mechanisms underlying emergence from latency are poorly understood. In this study, we determined the contribution of the transcription factors NF‐κB, NFAT, and AP‐1 in the reactivation of latent HIV following T‐cell receptor (TCR) activation using Jurkat T‐cell clones harboring single latent HIV proviruses. Our findings demonstrate that during reactivation from latency, NF‐κB enhances HIV transcription while NFAT inhibits it by competing with NF‐κB for overlapping binding sites on the HIV long terminal repeat (LTR). We have also demonstrated for the first time the molecular contribution of AP‐1 in the reactivation of HIV from latency, whereby AP‐1 synergizes with NF‐κB to regulate HIV transcriptional elongation following TCR activation.