Such inhibition was nearly restored by a retinoid X receptor (RXR) antagonist. Peretinoin had no effect on either HCV translation or activation of cellular IFN signaling and Peretinoin-resistant HCV mutants did not emerge after long culture of HCV-replicating cells with Peretinoin. Interestingly, Peretinoin dramatically reduced the numbers of lipid droplets (LDs), triglyceride abundance, and the expression of mature sterol regulatory this website element-binding protein 1c and fatty acid synthase. As lipids including LDs and triglyceride have been reported to be important for efficient infectious virus production, Peretinoin dramatically reduced

infectious virus production by specifically inhibiting HCV virus secretion without affecting either assembly or entry of virus. [Conclusions] Peretinoin alters lipid metabolism and inhibits HCV RNA replication and virus release through RXR signaling. These effects may be beneficial in addition to its potential mTOR inhibitor for chemoprevention of HCC in HCV-infected patients. Disclosures: Stanley M. Lemon – Advisory Committees or Review Panels: Merck, Santaris, Abbott, Gilead; Consulting: Achillion, Idenix; Grant/Research Support: Merck, Tibotec, Scynexis; Speaking and Teaching: Hoffman LaRoche Shuichi Kaneko – Grant/Research Support: MDS, Co., Inc, Chugai Pharma., Co., Inc, Toray Co., Inc, Daiichi Sankyo., Co., Inc,

Dainippon Sumitomo, Co., Inc, Ajinomoto Co., Inc, MDS, Co., Inc, Chugai Pharma., Co., Inc, Toray Co., Inc, Daiichi Sankyo., Co., Inc, Dainippon Sumitomo, Co., Inc, Ajinomoto Co., Inc, Bayer Japan The following people have nothing to disclose: Tetsuro Shimakami, Masao Honda, Takayoshi Shirasaki Background: Alpha interferon (IFN), a type I cytokine, plays a major role in the antiviral treatment of chronic hepatitis C virus (HCV) infection. IFN modulates the innate immune response and exerts a direct antiviral mechanism by activating

more than 500 intracellular genes. Many studies identified genes implicated in the IFN response in hepatoma cell lines infected by the HCV strain JFH1, such as PDIP1 (PPAR-gamma DNA-binding domain-interacting protein 1) (Fusco et al. Gastroenterology 2013). Objective: The aim of this study was to selleck products elucidate the role of PDIP1 in the antiviral mechanisms of IFN during HCV JFH1 infection of Huh7.5.1 cells, a human hepatoma cell line. Methods & Results: Treatment of j FH1-infected Huh7.5.1 cells with different PPAR alpha and gamma ligands including MK886, GW6471 and CP868388 showed a dose-dependent antiviral effect, in the absence of cell toxicity measured by luminescent cell viability assay (CellTiter-GIo®). These PPAR ligands were able to reduce the proportion of core-positive cells by at least 70% compared to vehicle-treated control cells. To investigate at which step(s) of the viral lifecycle PPAR alpha ligands were capable of inhibiting JFH1 infection, Huh7.5.