COCAINE AND HIV-1 REGULATE ASTROCYTE MITOCHONDRIAL ANTIVIRAL SIGNALING PROTEIN (MAVS) MEDIATED INFLAMMATION

Cocaine is a highly addictive psychostimulant estimated to have been used by 14.9% of Americans. Once in the central nervous system (CNS), cocaine increases the progression of viral infections, like human immunodeficiency virus (HIV-1) and exacerbates the development of HIV-associated neurocognitive disorders (HAND). Cocaine impacts antiviral immune responses promoting increased inflammation. We previously demonstrated that cocaine increases DNA damage via oxidative stress and increases astrocyte antiviral immune responses. However, the mechanism by which cocaine induced antiviral responses remained unclear, necessitating further research. This work aimed to address the gap in understanding whether mitochondrial antiviral signaling protein (MAVS) mediates the mechanism by which cocaine induces antiviral responses. MAVS is a vital part of our innate immune system that responds to viral perturbation, chemical hypoxia, host cell injury and metabolic perturbations. We investigated the role of the MAVS pathway in cocaine and HIV-1 mediated astrocyte inflammation because previous work has shown that cocaine significantly increases reactive oxygen species (ROS) and self-DNA damage both of which can mediate MAVS. Our results show that cocaine trends towards reducing astrocyte viability and increasing nuclear and mitochondrial DNA damage. Cocaine causes significant increases in MAVS aggregation and primes the MAVS pathway for inflammation. We demonstrate that HIV-1 mediated astrocyte inflammation is regulated partially via MAVS. Our research shows that MAVS is a mechanism by which cocaine primes and HIV-1 mediates astrocyte pro-inflammatory responses that contribute to inflammation in the CNS. The CNS is particularly vulnerable to damage when chronically subjected to inflammation and prolonged CNS inflammation is known to cause neurodegeneration. Our findings are valuable because cocaine use is often comorbid with HIV-1 infection, and the priming of MAVS by cocaine may be the mechanism driving the deleterious neurological outcomes seen in people living with HIV-1 who also use cocaine.

Name thesis:degree_name

Human Pathophysiology and Translational Medicine (Doctoral)

Grantor

The University of Texas Medical Branch at Galveston

Year dc:date.issued

2025

Author dc:creator

• Ledoux, Camille May 1999-

Advisor dc:contributor.advisor

• Cisneros, Irma (iricisner@utmb.edu)

Committee members dc:contributor.committeemember

• Slobodan Paessler
• Jerel Fields
• Patrick Hornak
• Monique Pappadis

Language dc:language.iso

English

Handle dc:identifier.uri

https://hdl.handle.net/2152.3/12835

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/12835