Ribavirin Pretreatment Improves the IFN-γ Response of Natural Killer Cells to IFN-based Therapy of Hepatitis C Virus Infection

Ribavirin is an important component of interferon-based and direct antiviral treatment regimens of hepatitis C virus (HCV) infection. Immunomodulation, in particular improvement of the host interferon response, has been proposed as a mechanism of action. Natural killer (NK) cells are sensitive biomarkers for IFN-α/β receptor signaling, as NK cell cytotoxicity and IFN-γ production are regulated by STAT1- and STAT4-phosphorylation, respectively. Upon continued exposure to IFN-α, an increase in STAT1 levels limits STAT4 access at the IFN-α/β receptor and results in decreased IFN-γ production. Accordingly, NK cell I…