{"doi":"10.3389/fimmu.2021.760707","title":"Oxidative Stress Induces Mitochondrial Compromise in CD4 T Cells From Chronically HCV-Infected Individuals","abstract":"We have previously shown that chronic Hepatitis C virus (HCV) infection can induce DNA damage and immune dysfunctions with excessive oxidative stress in T cells. Furthermore, evidence suggests that HCV contributes to increased susceptibility to metabolic disorders. However, the underlying mechanisms by which HCV infection impairs cellular metabolism in CD4 T cells remain unclear. In this study, we evaluated mitochondrial mass and intracellular and mitochondrial reactive oxygen species (ROS) production by flow cytometry, mitochondrial DNA (mtDNA) content by real-time qPCR, cellular respiration by seahorse analyzer, and dysregulated mitochondrial-localized proteins by Liquid Chromatography-Mass Spectrometry (LC-MS) in CD4 T cells from chronic HCV-infected individuals and health subjects. Mitochondrial mass was decreased while intracellular and mitochondrial ROS were increased, expressions of master mitochondrial regulators peroxisome proliferator-activated receptor 1 alpha (PGC-1α) and mitochondrial transcription factor A (mtTFA) were down-regulated, and oxidative stress was increased while mitochondrial DNA copy numbers were reduced. Importantly, CRISPR/Cas9-mediated knockdown of mtTFA impaired cellular respiration and reduced mtDNA copy number. Furthermore, proteins responsible for mediating oxidative stress, apoptosis, and mtDNA maintenance were significantly altered in HCV-CD4 T cells. These results indicate that mitochondrial functions are compromised in HCV-CD4 T cells, likely via the deregulation of several mitochondrial regulatory proteins.","journal":"Frontiers in Immunology","year":2021,"id":180880,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","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":336315,"name":"Dechao Cao","orcid":"0000-0001-5038-1807","position":4,"is_corresponding":false},{"id":338131,"name":"Xindi Dang","orcid":null,"position":5,"is_corresponding":false},{"id":336317,"name":"Sushant Khanal","orcid":"0000-0001-8028-6034","position":6,"is_corresponding":false},{"id":482838,"name":"Jinyu Zhang","orcid":"0000-0002-9200-5348","position":7,"is_corresponding":false},{"id":103949,"name":"Yi Zhang","orcid":"0000-0001-9861-4681","position":8,"is_corresponding":false},{"id":338133,"name":"Xiao Y. Wu","orcid":null,"position":9,"is_corresponding":false},{"id":336322,"name":"Shunbin Ning","orcid":"0000-0001-5484-5779","position":10,"is_corresponding":false},{"id":338135,"name":"Mohamed El Gazzar","orcid":null,"position":11,"is_corresponding":false},{"id":336323,"name":"Jonathan P. Moorman","orcid":"0000-0002-6102-6541","position":12,"is_corresponding":false},{"id":336324,"name":"Zhi Q. Yao","orcid":"0000-0002-1848-1071","position":13,"is_corresponding":false},{"id":336311,"name":"Madison Schank","orcid":"0000-0001-9017-3180","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:48:01.257885Z","pmid":"34956192","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":[]}