Characterization of host proteins that participate in the replication of hepatitis C virus (HCV)

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Hepatitis C virus (HCV) is a major agent of liver disease in man. There are no efficient vaccination procedures available and current therapies fail with a large group of patients. Thus, unraveling the molecular basis of the viral replication process is important to understand the mechanisms of viral pathogenesis and to improve the treatment of hepatitis C. Our proposal aims at identifying and functionally characterizing cellular proteins, which, besides hitherto known `host factors¿, support the replication of the HCV RNA genome in the cell¿s cytoplasm and to achieve further insights into the physical organization of the viral replication complex (RC). Recent studies revealed the existence of a high molecular weight cytoplasmic complex that contains HCV host factors such as the hVAP-A protein and the so-called NFAR proteins as well as various undetermined proteins. Considering this complex a likely intermediate of the viral RC it will be purified and its protein components identified by mass-spec analysis. Newly recognized proteins will be tested in terms of a potential role in the intracellular translation and replication cycle of the HCV RNA and the molecular detail of protein-protein interactions analyzed by genetic and biochemical means. Along these lines, we anticipate gaining vital information on the composition of the viral replication machinery and to expand our knowledge on pathogenic features of HCV that are caused by the viral recruitment of cellular components.