Ribavirin enhances interferon-stimulated gene transcription by activation of the interferon-stimulated response element.

摘要

Ribavirin, a synthetic nucleoside analogue, is used in combination with pegylated interferon-a (IFN-a) as the standard of care for the treatment of patients with chronic hepatitis C. The combination of ribavirin significandy improves the sustained virologic response of IFN-a therapy, but the exact mechanism remains enigmatic. Although ribavirin monotherapy appears to have only limited clinical efficacy,1'2 in vitro studies have shown that ribavirin by itself has a remarkable broad antiviral activity, equivalent to IFNs, against a spectrum of RNA and DNA viruses.3 Now, an exciting new study by Thomas et al. in Hepatology4 shows that ribavirin treatment induces the expression of particular IFN-stimulated genes (ISGs), including IRF7 and IRF9, thereby potentiating the antiviral action of IFN-a in hepatitis C virus (HCV) cell culture models. Because die transcription factors IRF7 and IRF9 are known to be critical for antiviral defenses, including against HCV, the authors conclude that antiviral action of ribavirin alone and in particular in combination with IFN-a4 acts via the induction of ISGs.