Abstract
A robust innate and adaptive immune response is essential to viral clearance. Hepatitis C virus (HCV) infection typically leads to alteration of the innate and adaptive immune response, which is caused by interaction of HCV core protein with various host factors. It is important to investigate the alterations to the immune response during the transition from acute HCV to chronic HCV infection to develop better therapeutic methods for HCV infection. In this work, to determine whether HCV viral persistence occurs via tumor necrosis apoptosis-inducing ligand (TRAIL)-mediated apoptosis, we stimulated peripheral blood mononuclear cells (PBMCs) with recombinant HCV core protein within 12 h to measure the relative expression of death receptors 4 and 5 (DR4 and DR5) in PBMCs. We show that recombinant HCV core protein causes increased DR4 and DR5 expression in PBMCs. We also show that TRAIL interacts with DR4 and DR5 after cleavage of membrane-bound TRAIL yielding soluble TRAIL. Our results show that HCV core protein increases PBMC susceptibility to apoptosis and may cause increased TRAIL pathway activity within 12 h of infection. In addition, we observed that increased death receptor expression may contribute to HCV pathogenesis, as typically observed in chronically HCV-infected individuals.
