Interference of HCV with inflammatory effector systems

This project focuses on the molecular elucidation of hepatitis C virus “stealth” – mechanisms which antagonize elimination of the virus, modulate host cell immune functions and lead to a high rate of chronic infections. During the current funding period it could be shown that HCV modifies Akt mediated growth factor signaling by NS3/4A dependent cleavage of the T-cell protein tyrosine phosphatase (TC-PTP) and that this cleavage as well as the tyrosine kinase c-Src is crucial for viral replication. Moreover, results of the project indicate that HCV or expression of the isolated NS3/4A protein influences basal and induced cytokine/chemokine expression in vitro and in vivo. Furthermore, it could be demonstrated that HCV induces degradation of different members of the inhibitor of kappa B family. In the coming funding period the importance of these observations for HCV induced chemokine synthesis will be addressed as well as the underlying molecular mechanism responsible for HCV mediated degradation of the different IκB molecules. Furthermore the influence of HCV mediated TC-PTP suppression and enhancement of p38MAPK activity on the basal and cytokine induced chemokine production of hepatocytes will be
assessed.

PD Dr. Johannes Bode, Prof. Dr. med. Dieter Häussinger
Department of Gastroenterology, Hepatology and Infectiology Heinrich-Heine-University of Düsseldorf



TP7 in period 2007-2009

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