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J. Virol. doi:10.1128/JVI.00795-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Bile Acids Promote the Expression of Hepatitis C Virus in Replicon-Harboring Cells

Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506

^* To whom correspondence should be addressed. Email: kchang{at}vet.ksu.edu.

	Abstract

Hepatitis C virus (HCV) is a cause of chronic liver disease, with more than 170 million persistently infected individuals worldwide. Although the combination therapy of interferon(IFN)- and ribavirin is effective for the chronic HCV infection, around half of patients infected with HCV genotype 1 fail to show a sustained virologic response and remain chronically infected. Previously, we demonstrated that bile acids were essential for the growth of porcine enteric calicivirus in cell culture in association with the down-regulation of the IFN responses. Because hepatocytes are exposed to high concentrations of bile acids in the liver, we hypothesized that bile acids have similar effects on HCV replication. We incubated HCV replicon-harboring cells (genotype 1b, Con1) in the presence of various bile acids and monitored the expression of HCV RNA and protein (NS5B). The addition of an individual bile acid (deoxycholic aicd, chenodeoxycholic acid, ursodeoxycholic acid, or glycochenodeoxycholic acid) in the medium increased the levels of HCV RNA and proteins up to 5-fold at 48 h of incubation. An antagonist of bile acid receptor farnesoid X receptor, Z-guggulsterone, reduced the bile acid-mediated increase of HCV RNA. When IFN ( or ) and each bile acid were incubated together, we observed that bile acid significantly reduced the anti-HCV effect of IFN. These results indicated that bile acids are factors for the failure of IFN treatment in certain patients infected with HCV genotype 1. Our finding may also contribute to the establishment of better regimens for treatment of chronic HCV infections by including agents altering bile acid-mediated FXR pathway.

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