Institute of Biomedical Sciences

Title

Role of Mitochondrial Antiviral Signaling Protein in Reactivation of Latent HIV-1 in CD4+ T cells

Poster Number

13

Document Type

Poster

Status

Graduate Student - Doctoral

Abstract Category

HIV/AIDS

Keywords

ROS, mitochondria, HIV latency, MAVS

Publication Date

Spring 2018

Abstract

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.

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. We have shown that chemical activation of MAVS, triggered by reactive oxygen species 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. 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.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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Role of Mitochondrial Antiviral Signaling Protein in Reactivation of Latent HIV-1 in CD4+ T cells

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.

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. We have shown that chemical activation of MAVS, triggered by reactive oxygen species 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. 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.