[摘要]：Background. The manner in which ribavirin (RBV) enhances the antiviral effects of interferon (IFN) against hepatitis C virus (HCV) remains unknown. We investigated whether RBV modifies IFN-stimulated genes (ISGs) in vivo and in vitro. Methods. We measured the messenger RNA (mRNA) levels of ISGs in T lymphocytes from patients with HCV infection who were receiving IFN-alpha therapy with or without RBV. We added RBV and/or IFN-alpha to a plasmid-based HCV replication system containing a full-length HCV genotype la sequence in HepG2 and Huh7 cell lines and the JFH-1 HCV genotype 2a sequence in Huh7 cell lines and measured levels of ISGs and autocrine IFN-beta. Results. The expression of protein kinase R and myxovirus resistance A mRNA was enhanced more with IFN-alpha and RBV than by IFN-alpha alone in assays in vivo and in vitro. Such enhancement depended on autocrine IFN-beta being enhanced by RBV. RBV upregulated interleukin 8 (IL-8) in the absence of IFN-alpha. The IL-8 upregulation induced by RBV was responsible for the activation of activator protein 1 (AP-1). Conclusions. Ribavirin augments the anti-HCV effects of IFN-alpha induced by ISGs through enhancing autocrine IFN-beta. Moreover, RBV can enhance IL-8 through activating AP-1. Improved understanding of ISG modulation by RBV would help to establish a means of eliminating HCV.
