Renilla luciferase

activity and HCV core immune staining confirm that HCV replication was undetectable after repeated treatment with IFNλ but not IFN α and IFN . Furthermore, IFN λ induce Stat 1, Stat 2, Stat 3 phosphorylation and nuclear translocation in IFN a resistant FFA HCV cell culture. Pretreatment of Jak1 inhibitor (Pyridone 6) prevented the antiviral activity of interferon lambda against HCV in free fatty acid culture Conclusion: IFN γclears HCV replication and overcome HCV resistance to IFN a in FFA cell culture model by initiating Stat 1, Stat 2, PI3K inhibitor and Stat phosphorylation and their nuclear translocation. Our findings show that IFN is a better choice for treatment of HCV infection.

Disclosures: Nathan J. Shores – Advisory Committees or Review Panels: Gilead; Speaking and Teaching: Vertex, Merck, Salix Luis A. Balart – Advisory Committees or Review Panels: Genentech, Genentech; Grant/Research Support: Merck, Genentech, Bayer, conatus, Ocera, Hyperion, Gilead Sciences, Bristol Myers Squibb, Mochida, Eisai, Vertex, Merck, Genentech, Bayer, Conatus, Ocera, Hyperion, Gilead Sciences, Bristol Myers Squibb, Mochida, Eisai, selleck kinase inhibitor Vertex, takeda, GI Dynamics; Speaking and Teaching: Merck, Merck, Merck, Merck The following people have nothing to disclose: Ramazan Kurt, Partha K. Chandra, Fatma Aboulnasr, Rajesh Panigrahi, Pauline Ferraris, Srikanta Dash [Background and Aims] An oral acyclic retinoid, Peretinoin, was shown to significantly reduce the incidence of post-therapeutic hepatocellular carcinoma 上海皓元 (HCC) recurrence and improve the survival rates of patients in a clinical trial (NEJM, 1996, 1999), and larger-scale clinical studies are ongoing in various countries to confirm its clinical efficacy. Hepatitis C Virus (HCV) is known as a major causative pathogen of HCC. Therefore, depending on the results of clinical

studies, Peretinoin may be used for HCV-infected patients as a chemo preventive drug for HCC. However, the precise mechanisms of Peretinoin on HCV life cycle have not been evaluated. Here, we extensively examined the effect of retinoids including Peretinoin on HCV infection in cultured cells. [Methods] The Effects of several retinoids, such as Peretinoin, 9-cis retinoic acid (9-cis RA), 13-cis RA, and all-trans retinoic acid, on HCV RNA replication in cultured cells were examined by using different HCV genomes (genotypes 1a, 1b, and 2a) encoding the Gaussia luciferase reporter protein. The mechanisms of its inhibitory effect on HCV infection were assessed by evaluating cellular signaling pathways, such as interferon and lipid metabolism, and various aspects of HCV life cycle, such as virus translation, RNA amplification, infectious virus production including assembly, secretion, and entry.