Interleukin-28b: A Key Piece of the Hepatitis C Virus Recovery Puzzle

HCV RNA triggers production of type 1 interferons (such as interferon β and interferon α) and probably lambda interferons by hepatocytes, and these molecules (and probably the virus itself) stimulate transcription of interferon stimulated genes (ISGs) in antigen presenting cells such as dendritic cells as well as in hepatocytes. Exogenous (therapeutic) interferon α and lambda interferon signal similarly, but in a “steady-state” environment in which HCV replication has been sustained despite ongoing expression of ISGs. Polymorphisms just upstream of the gene for IL-28b (interferon lambda 3) are strongly associated with spontaneous and treatment-associated resolution of HCV infection, but the mechanism is unknown.