Chronic HCV infection promotes cytotoxicity in antigen-specific CD8+ T cells regardless of virus specificity

Introduction 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 complete understanding the factors driving an effective response contributes to failure develop vaccine for prevention. This study advances existing knowledge HCV-specific CD8 + T cells describes impact current or past specific other viruses. Methods We used barcoded-dextramers identify sort HCV, cytomegalovirus, influenza, characterized them using single-cell RNA sequencing technology. Our cohort included chronic (cHCV), spontaneously resolved (rHCV), subjects undergoing direct-acting antiviral (DAA) therapy. Results show that have cytotoxic features patients with cHCV, which is progressively reduced DAA therapy persists 12 weeks after treatment completion. also observe shift cell phenotype decreased effector memory exhausted signatures. In rHCV, we detected smaller proportion compared cHCV. The cHCV rHCV was comparable. Moreover, observed non-HCV virus-specific exhibit robust traits during infection. Discussion Altogether, our findings suggest promotes cytotoxicity regardless specificity. immunological changes caused by may contribute worsening ongoing damage exacerbate possible co-infections. data provide resource groups exploring underlying mechanisms spontaneous treatment-induced resolution inform development vaccines against