Hepatitis C virus (HCV), a member of the Flavivirideae family, contains a positive single-stranded RNA genome that also functions as mRNA. Approximately 4 million persons in the United States and probably more than 100 million people worldwide are infected with hepatitis C virus (HCV). The virus has the unique ability to cause persistent infection in susceptible hosts after parenteral or percutaneous transmission. The immunologic correlates of protection and viral clearance and the pathogenesis of liver injury are yet to be defined. Nearly 70% to 80% of infected persons become chronic carriers, and chronic and progressive HCV infection carries significant morbidity and mortality (e.g., major cause of cirrhosis, end-stage liver disease, and liver cancer).
Currently, the only approved therapy for treatment of chronic HCV infection is a 24-48 week course of the combination of type I interferon (IFNα/β) and ribavirin with sustained viral clearance observed in 42% to 82% of treated individuals. Unfortunately this treatment is problematic due to considerable deleterious side effects. Ribavirin causes dose-related hemolysis and anemia, with severe side effects frequently observed with combination therapy. In many cases, treatment has to be reduced to mono-therapy with interferon alone.
The mechanism(s) of actions of IFN (or resistance to IFN) during antiviral therapy for HCV and other RNA viruses are not well understood, although such an understanding is desirable to guide development of new antiviral treatments.