EASL- COFFEE INTERFERES WITH HCV REPLICATION IN VITRO BY INHIBITION OF WNT SIGNALING

Title	COFFEE INTERFERES WITH HCV REPLICATION IN VITRO BY INHIBITION OF WNT SIGNALING
Speaker:	Amelie Keller
Author:	A.D. Keller1*, K. Singethan2, A. Wuestenberg1, V. Lohmann3, R. Bartenschlager3, M. Dandri4, U. Protzer2, G. Tiegs1, G. Sass1
Affiliation:	1Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg Eppendorf, Hamburg, 2Institute of Virology, Technische Universität München (TUM), Munich, 3Department of Molecular Virology, University of Heidelberg, Heidelberg, 4Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. *amelie_keller@web.de
Background and aims:  Coffee is the worldwide most frequently used legal psychoactive substance. On the other hand its consumption has been shown to decrease the risk of fibrosis formation and to improve anti-viral effects of interferon alpha/ribavirin treatment of HCV patients. We investigated effects of regular and decaffeinated coffee and coffee ingredients on HCV replication and infection in vitro. Methods:  To investigate effects of coffee on HCV replication, infectious as well as subgenomic replicon cell culture systems were used. Cells were incubated in the presence of regular or decaffeinated coffee or the coffee ingredients caffeine or chlorogenic acid. Effects on HCV replication and wnt pathway activity were measured by luciferase reporter assay or real time RT-PCR. Results: Coffee reduced HCV replication with regular coffee having a more pronounced effect. Coffee significantly reduced HCV replication at concentrations achievable by coffee consumption, while caffeine as well as caffeine degradation products interfered with HCV replication at high concentrations (about 100 µM or more). Chlorogenic acid did not reduce HCV replication up to concentrations of 200 µM. Wnt pathway activity was found to be markedly increased in HCV replicating cells in comparison to the background cell line Huh7. Inhibition of wnt pathway activity, e.g. by use of siRNA directed against beta-catenin, interfered with HCV replication. Likewise, coffee-but not caffeine-incubation reduced wnt pathway activity, as detected by reporter assays or real time RT-PCR for beta-catenin, conductin or the wnt pathway promoter kinase CK2. In addition to its inhibitory effects on HCV replication, two hours of pre-incubation with coffee decreases subsequent HCV infection and modulated HCV receptor expression on primary human hepatocytes. Conclusions:  Coffee interferes with HCV replication by inhibition of the wnt signaling pathway which might represent a novel target for HCV therapy. Coffee also interferes with HCV infection in vitro which might reduce virus spreading within the infected liver. http://mobile.ilcapp.eu/EASL_161/poster_24038/program.aspx