Activation of the Anti-Oxidative Stress Response Reactivates Latent HIV-1 Through the Mitochondrial Antiviral Signaling Protein Isoform MiniMAVS
Year: 2021
Type: article
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.
Source: Frontiers in Immunology
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: U.S. Department of Defense, University of Utah, Case Western Reserve University, National Institutes of Health, Center for AIDS Research, University of Washington, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: Mechanisms Governing Latency in Clinically Relevant HIV-1 Strains, G1589278233, G3072202247, G3364798494, G3608974278, G3646000930, Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV (CHEETAH Center), G4119534169, G5374675963, Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV (CHEETAH Center), Preclinical Development of Ingenol and HDACi Toward HIV Eradication, G5850682332, G6812101401, Tyrosine Kinase inhibition: The New Front in HIV Cure Efforts, US MILITARY HUMAN IMMONODEFIECIENCY VIRUS (HIV) RESEARCH PROGRAM, Reactivation of latent HIV through TLR signaling, CRISPR/Cas9 technology toward understanding HIV latency in primary cells, Developing Pathogen Recognition Receptor Agonists as Latency Reversing Agents, G9000054667, G9000054902, G9000110273, G9000273067, District of Columbia Center for AIDS Research, Cancer Center Support Grant
OpenAlex ID: W3167384356