HCV-core and NS3 antigens play disparate role in inducing regulatory or effector T cells in vivo: Implications for viral persistence or clearance

A distinguishing feature of HCV is its ability to persist in majority of the infected people. We investigated the role of HCV-core and NS3 in inducing effector T cells to mediate antiviral immunity. Our studies revealed that immunization with recombinant adenoviral vector containing HCV-core or NS3 leads to differential development of regulatory vs. effector T cells in mice, resulting in distinct outcomes of virus infection. For the first time, our studies directly demonstrate that HCV-core enhances both CD4+ and CD8+ Tregs which possibly contribute to persistent infection, whereas HCV NS3 induces both CD4+ and CD8+ effector T cells to allow viral clearance.