The various genotypes interact differently with the host immune system, though the molecular basis for this is unclear. Chronic infection by genotypes 1 and 4 is notoriously resistant to treatment with IFN, while genotypes 2 and 3 have relatively better responses. This difference may be in part due to mutations in the NS5A protein. In cellular models NS5A can interact with IFN-induced antiviral enzymes such as 2’5’OAS. Other HCV proteins likely interact with cellular proteins to alter responses to immune and IFN antiviral mechanisms: HCV core protein dampens lymphocytic Th1 responses and influences IRF, Jak/STAT and iNOS pathways. Although these results suggest how the virus may alter known cellular pathways, viral evasion of the immune system is multifactorial and clearly complex.