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Molecular analysis of hepatitis C virus - dendritic cell interaction

Applicant Dr. Heidi Barth
Subject Area Virology
Term from 2007 to 2010
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 46424334
 
With an estimated 170 million infected individuals worldwide, hepatitis C virus (HCV) has a major impact on public health. Treatment options are limited and a vaccine for prevention against HCV infection is not available. Dendritic cells (DCs) play as antigen-presenting cells a crucial role in the generation and regulation of anti-viral immunity. Successful viral clearance of HCV is mainly associated with a strong and maintained HCV-specific CD4+ and CD8+ T cell response indicating efficient T cell priming by DCs. However, infection by HCV is characterized by its high tendency to chronicity. The mechanisms by which HCV establishes persistence and the role of DCs in this process are unkown. Efforts to understand the interaction of HCV with DCs have been hampered for a long time due to the difficulties to synthesize and purify sufficient quantities of infectious virions. Most recently, several laboratories succeeded in establishing a robust HCV cell culture infection system based on a clone derived from a viral isolate of a Japanese patient with fulminant hepatitis C, that allows the production of high titre infectious virus*. Aiming to understand the immunopathogenesis of an HCV infection, this project will focus on the molecular analysis of HCV recognition, uptake and presentation by DCs as well as study effects of HCV on DC function. The identification of molecular mechanisms required for HCV processing and presentation by DCs will contribute significantly to the understanding of HCV immunopathogenesis and may finally contribute to the development of preventive and/or therapeutic vaccine strategies.
DFG Programme Research Fellowships
International Connection France, USA
 
 

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