Work

Role of mitochondrial antiviral signaling protein in reactivation of latent HIV-1 in CD4+ T cells

Year: 2017

Type: article

Abstract: Background: The mitochondrial antiviral signaling protein (MAVS) is involved in response to viral infection, and mediates signaling that culminates in type I interferon production and activation of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB).HIV-1 has NF-κB binding sites in its long terminal repeat, allowing it to use NF-κB for viral transcription.We hypothesize that stimulation of MAVS in CD4+ T cells can reactivate latent HIV-1, and investigated the potential of targeting MAVS as a latency reversing strategy.Methods: To assess MAVS stimulation as a potential strategy for reactivation, we have used a primary CD4+ T cell model which recapitulates latency in vitro, as well as resting CD4+ T cells from aviremic participants.We also employed a CRISPR/Cas9 strategy to study the role MAVS plays in viral reactivation using the latent HIV-1 model JLAT 10.6.Results: We have shown that chemical activation of MAVS, triggered by reactive oxygen species, or endoplasmic reticulum (ER) stress is sufficient to reactivate latent HIV-1.Interestingly, we have found that several widely studied latency-reversing agents (LRAs) mediate their effect partly through the activation of MAVS.Conclusions: Our results show that targeting MAVS in latently infected HIV-1 cells can lead to viral reactivation.Thus, MAVS is a potential therapeutic target for reversing HIV-1 latency.PP 9.

Source: Journal of Virus Eradication

DOI: 10.1016/s2055-6640(20)30676-2