{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/12835"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/12835","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"title":"COCAINE AND HIV-1 REGULATE ASTROCYTE MITOCHONDRIAL ANTIVIRAL SIGNALING PROTEIN (MAVS) MEDIATED INFLAMMATION","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Ledoux, Camille May 1999-"],"institution":"The University of Texas Medical Branch at Galveston","degree_name":"Human Pathophysiology and Translational Medicine (Doctoral)","degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Cisneros, Irma (iricisner@utmb.edu)"],"committee_chairs":[],"committee_members":["Slobodan Paessler","Jerel Fields","Patrick Hornak","Monique Pappadis"],"year":2025,"date_issued":"2025-05","date_published":"2025-05","updated_at":"2026-07-24T05:51:04Z","subjects":[],"languages":["English"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2152.3/12835","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Cisneros, Irma (iricisner@utmb.edu)"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Slobodan Paessler","Jerel Fields","Patrick Hornak","Monique Pappadis"]},{"key":"dc:creator","label":"Author","values":["Ledoux, Camille May 1999-"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2026-04-01T18:55:27Z"]},{"key":"dc:date.issued","label":"Date","values":["2025-05"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Human Pathophysiology and Translational Medicine (Doctoral)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas Medical Branch at Galveston"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["English"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/2152.3/12835"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["COCAINE AND HIV-1 REGULATE ASTROCYTE MITOCHONDRIAL ANTIVIRAL SIGNALING PROTEIN (MAVS) MEDIATED INFLAMMATION"]}]}],"canonical_facts":{"dc:contributor.advisor":["Cisneros, Irma (iricisner@utmb.edu)"],"dc:contributor.committeemember":["Slobodan Paessler","Jerel Fields","Patrick Hornak","Monique Pappadis"],"dc:creator":["Ledoux, Camille May 1999-"],"dc:date.accessioned":["2026-04-01T18:55:27Z"],"dc:date.issued":["2025-05"],"dc:description.abstract":["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."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://hdl.handle.net/2152.3/12835"],"dc:language.iso":["English"],"dc:title":["COCAINE AND HIV-1 REGULATE ASTROCYTE MITOCHONDRIAL ANTIVIRAL SIGNALING PROTEIN (MAVS) MEDIATED INFLAMMATION"],"dc:type":["Thesis"],"thesis:degree_name":["Human Pathophysiology and Translational Medicine (Doctoral)"],"thesis:institution_name":["The University of Texas Medical Branch at Galveston"]},"updated_at":"2026-07-24T05:51:04Z"}