{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:15:19Z","timestamp":1791404119113,"version":"4.3.3"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK117004, DK106491, P30DK048522"],"award-info":[{"award-number":["DK117004, DK106491, P30DK048522"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Virol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Despite advancements in hepatitis C virus (HCV) infection treatment, HCV still represents a significant public health burden. Besides progressive hepatic damage, viral persistence has lasting effects on innate and adaptive immune responses. Lack of a complete understanding of the factors driving an effective HCV response contributes to the failure to develop a vaccine for prevention. This study advances the existing knowledge on HCV-specific CD8<jats:sup>+<\/jats:sup> T cells and describes the impact of current or past HCV infection on CD8<jats:sup>+<\/jats:sup> T cells specific for other viruses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used barcoded-dextramers to identify and sort CD8<jats:sup>+<\/jats:sup> T cells specific for HCV, cytomegalovirus, and influenza, and characterized them using single-cell RNA sequencing technology. Our cohort included chronic (cHCV), spontaneously resolved (rHCV), and subjects undergoing direct-acting antiviral (DAA) therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We show that HCV-specific CD8<jats:sup>+<\/jats:sup> T cells have cytotoxic features in patients with cHCV, which is progressively reduced with DAA therapy and persists 12 weeks after treatment completion. We also observe a shift in the CD8<jats:sup>+<\/jats:sup> T cell phenotype on DAA treatment, with decreased effector memory and exhausted cell signatures. In rHCV, we also detected a smaller proportion of effector memory cells compared to cHCV. The proportion of CD8<jats:sup>+<\/jats:sup> exhausted T cells in cHCV and rHCV subjects was comparable. Moreover, we also observed that non-HCV virus-specific CD8<jats:sup>+<\/jats:sup> T cells exhibit robust cytotoxic traits during cHCV infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Altogether, our findings suggest that cHCV infection promotes cytotoxicity in CD8<jats:sup>+<\/jats:sup> T cells regardless of virus specificity. The immunological changes caused by cHCV infection in CD8<jats:sup>+<\/jats:sup> T cells may contribute to worsening the ongoing hepatic damage caused by HCV infection or exacerbate the immune response to possible co-infections. Our data provide a resource to groups exploring the underlying mechanisms of HCV-specific T cell spontaneous and treatment-induced resolution to inform the development of effective vaccines against HCV infection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fviro.2023.1198361","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T05:12:49Z","timestamp":1687842769000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Chronic HCV infection promotes cytotoxicity in antigen-specific CD8+ T cells regardless of virus specificity"],"prefix":"10.3389","volume":"3","author":[{"given":"Ana C.","family":"Maretti-Mira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Salomon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela 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