@ARTICLE{10.3389/fimmu.2021.682182, AUTHOR={Sarabia, Indra and Novis, Camille L. and Macedo, Amanda B. and Takata, Hiroshi and Nell, Racheal and Kakazu, Juyeon C. and Furler, Robert L. and Shakya, Binita and Schubert, Heidi L. and Hill, Christopher P. and DePaula-Silva, Ana Beatriz and Spivak, Adam M. and Trautmann, Lydie and Planelles, Vicente and Bosque, Alberto}, TITLE={Activation of the Anti-Oxidative Stress Response Reactivates Latent HIV-1 Through the Mitochondrial Antiviral Signaling Protein Isoform MiniMAVS}, JOURNAL={Frontiers in Immunology}, VOLUME={12}, YEAR={2021}, URL={https://www.frontiersin.org/articles/10.3389/fimmu.2021.682182}, DOI={10.3389/fimmu.2021.682182}, ISSN={1664-3224}, ABSTRACT={The mitochondrial antiviral signaling protein (MAVS) is part of the cell’s innate immune mechanism of defense. MAVS mRNA is bicistronic and can give rise to a full length-MAVS and a shorter isoform termed miniMAVS. In response to viral infections, viral RNA can be sensed by the cytosolic RNA sensors retinoic acid-inducible gene I (RIG-I) and/or melanoma differentiation-associated protein 5 (MDA5) and activate NF-κB through interaction with MAVS. MAVS can also sense cellular stress and activate an anti-oxidative stress (AOS) response through the activation of NF-κB. Because NF-κB is a main cellular transcription factor for HIV-1, we wanted to address what role MAVS plays in HIV-1 reactivation from latency in CD4 T cells. Our results indicate that RIG-I agonists required full length-MAVS whereas the AOS response induced by Dynasore through its catechol group can reactivate latent HIV-1 in a MAVS dependent manner through miniMAVS isoform. Furthermore, we uncover that PKC agonists, a class of latency-reversing agents, induce an AOS response in CD4 T cells and require miniMAVS to fully reactivate latent HIV-1. Our results indicate that the AOS response, through miniMAVS, can induce HIV-1 transcription in response to cellular stress and targeting this pathway adds to the repertoire of approaches to reactivate latent HIV-1 in ‘shock-and-kill’ strategies.} }