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

FEBS Letters

article

Joseph Hokello¹  Adhikarimayum Lakhikumar Sharma²  Mudit Tyagi² 

[1] Department of Basic Science, Faculty of Science and Technology, Kampala International University Western Campus;Center for Translational Medicine, Thomas Jefferson University

关键词: HIV Latency;    HIV transcriptional elongation;    TCR activation;   

DOI  :  10.1002/1873-3468.14033

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown