Cumulative data derived from all three chimpanzees from 180 days of observation documented an inverse (negative) correlation between hepatic miR-122 and HCV RNA in the liver and serum and positive correlation between level of serum miR-122 and HCV replication. Thereafter, rise of miR-122 levels during HCV clearance selleck screening library and serum ALT normalization occurred. These data suggest a tri-phasic relationship among hepatic miR-122 expression, HCV replication and hepatic destruction. It was particularly apparent

in one chimpanzee. The findings imply complexities in the virus-host interaction during the acute phase of HCV infection. Disclosures: The following people have nothing to disclose: Youkyung Choi, Hans P. Dienes, Kris Krawczynski Background: Hepatitis C virus (HCV) chronically infects over 170 million people LY2157299 clinical trial worldwide and is a leading cause of cirrhosis and hepatocellular

carcinoma. The dependence of HCV on host lipid metabolism is extensive. We have previously reported that inhibition of HMG-CoA reductase suppresses HCV replication. It is not known whether HMG-CoA reductase inhibition also alters overall viral infectivity or changes the lipid composition of the virion particle. We sought to assess the effect of HMG-CoA reductase inhibition on other steps of the HCV lifecycle and on the lipid composition of HCV particles. Methods: Using liquid chromatography tandem mass spectrometry (LCMS), we performed lipidomic analyses of HCV particles. We also assessed the effect of HMG-CoA reductase inhibition on non-replicative HCV lifecycle steps. Results: In addition to decreasing HCV replication, inhibition Mannose-binding protein-associated serine protease of HMG-CoA reductase leads to the formation of HCV particles with impaired overall infectivity. These particles also exhibit decreased entry into hepatocytes. The lipidome of HCV particles is altered by HMGCoA reductase inhibition, resulting in lower cholesterol content with compensatory increases in other lipid species, including triacylglycerols, sphingomyelins, and phosphatidylcholines. Conclusions: HMG-CoA reductase

inhibition not only inhibits viral replication, but also alters the functional and physical properties of HCV particles. The decreased cholesterol content of the virions is the likely basis for their altered functional properties. These findings offer additional rationale for use of HMGR inhibitors as adjunctive, host targeted antivirals. Disclosures: Raymond T. Chung – Advisory Committees or Review Panels: Idenix; Consulting: Enanta; Grant/Research Support: Gilead, Merck, Mass Biologic, Gilead The following people have nothing to disclose: Lee F. Peng, James Meixiong, Amy Deik, Esperance A. Schaefer, Nikolaus Jilq, Pattranuch Chusri, Cynthia Brisac, Stephane Chevaliez, Chuanlonq Zhu, Jay Luther, Daniel Wambua, Dahlene N. Fusco, Wenyu Lin, Clary B.