AP‐1 and NF‐κB synergize to transcriptionally activate latent HIV upon T‐cell receptor activation

J Hokello, A Lakhikumar Sharma, M Tyagi - FEBS letters, 2021 - Wiley Online Library
FEBS letters, 2021Wiley Online Library
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 …
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.
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