{"doi":"10.3390/v15051061","title":"ROS-Induced Mitochondrial Dysfunction in CD4 T Cells from ART-Controlled People Living with HIV","abstract":"We have previously demonstrated mitochondrial dysfunction in aging CD4 T cells from antiretroviral therapy (ART)-controlled people living with HIV (PLWH). However, the underlying mechanisms by which CD4 T cells develop mitochondrial dysfunction in PLWH remain unclear. In this study, we sought to elucidate the mechanism(s) of CD4 T cell mitochondrial compromise in ART-controlled PLWH. We first assessed the levels of reactive oxygen species (ROS), and we observed significantly increased cellular and mitochondrial ROS levels in CD4 T cells from PLWH compared to healthy subjects (HS). Furthermore, we observed a significant reduction in the levels of proteins responsible for antioxidant defense (superoxide dismutase 1, SOD1) and ROS-mediated DNA damage repair (apurinic/apyrimidinic endonuclease 1, APE1) in CD4 T cells from PLWH. Importantly, CRISPR/Cas9-mediated knockdown of SOD1 or APE1 in CD4 T cells from HS confirmed their roles in maintaining normal mitochondrial respiration via a p53-mediated pathway. Reconstitution of SOD1 or APE1 in CD4 T cells from PLWH successfully rescued mitochondrial function as evidenced by Seahorse analysis. These results indicate that ROS induces mitochondrial dysfunction, leading to premature T cell aging via dysregulation of SOD1 and APE1 during latent HIV infection.","journal":"Viruses","year":2023,"id":335298,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":336312,"name":"Juan Zhao","orcid":"0000-0002-1809-3124","position":1,"is_corresponding":false},{"id":336313,"name":"Ling Wang","orcid":"0000-0001-7861-2769","position":2,"is_corresponding":false},{"id":338132,"name":"Lam Ngoc Thao Nguyen","orcid":null,"position":3,"is_corresponding":false},{"id":1064702,"name":"Yi Zhang","orcid":"0000-0001-7321-1202","position":4,"is_corresponding":false},{"id":338133,"name":"Xiao Y. Wu","orcid":null,"position":5,"is_corresponding":false},{"id":482838,"name":"Jinyu Zhang","orcid":"0000-0002-9200-5348","position":6,"is_corresponding":false},{"id":1064703,"name":"Yong Jiang","orcid":"0000-0002-3609-2280","position":7,"is_corresponding":false},{"id":336322,"name":"Shunbin Ning","orcid":"0000-0001-5484-5779","position":8,"is_corresponding":false},{"id":338135,"name":"Mohamed El Gazzar","orcid":null,"position":9,"is_corresponding":false},{"id":336323,"name":"Jonathan P. Moorman","orcid":"0000-0002-6102-6541","position":10,"is_corresponding":false},{"id":336324,"name":"Zhi Q. Yao","orcid":"0000-0002-1848-1071","position":11,"is_corresponding":false},{"id":336311,"name":"Madison Schank","orcid":"0000-0001-9017-3180","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-19T01:09:58.338267Z","pmid":"37243148","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}