Effect of ethanol on innate antiviral pathways and HCV replication in human liver cells.docVIP

Virology Journal BioMedCentral Research Open Access Effect of ethanol on innate antiviral pathways and HCV replication in human liver cells Courtney R Plumlee1,2, Catherine A Lazaro3, Nelson Fausto4 and Stephen J Polyak*5 Address: 1Department of Laboratory Medicine, University of Washington, Seattle, USA, 2Department of Biological Sciences, Columbia University, New York, NY, 3Department of Pathology, University of Washington, Seattle, USA, 4Department of Pathology, University of Washington, Seattle, USA and 5Departments of Laboratory Medicine, Microbiology and Pathobiology, University of Washington, Seattle, USA Email: Courtney R Plumlee - crp2109@; Catherine A Lazaro - clazaro@; Nelson Fausto - nfausto@; Stephen J Polyak* - polyak@ * Corresponding author Published: 02 December 2005 Received: 06 September 2005 Accepted: 02 December 2005 Virology Journal 2005, 2:89 doi:10.1186/1743-422X-2-89 This article is available from: /content/2/1/89 ? 2005 Plumlee et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. HCVIFNvirus-host interactionssignal transductionalcohol Abstract Alcohol abuse reduces response rates to IFN therapy in patients with chronic hepatitis C. To model the molecular mechanisms behind this phenotype, we characterized the effects of ethanol on Jak-Stat and MAPK pathways in Huh7 human hepatoma cells, in HCV replicon cell lines, and in primary human hepatocytes. High physiological concentrations of acute ethanol activated the Jak- Stat and p38 MAPK pathways and inhibited HCV replication in several independent replicon cell lines. Moreover, acute ethanol induced Stat1 serine phosphorylation, which was partially mediated by the p38 MAPK pathway. In contrast, when combined with exogenou