Cel Hepatitis C virus (HCV) is an important cause of worldwide liver disease. Current therapies are inadequate for most patients. Improving the understanding of the life cycle of this virus may provide opportunities for new antiviral strategies. Like all characterized positive-strand RNA viruses, HCV is also believed to replicate its RNA in association with intracellular membranes, the details of its replication complex assembly are unknown. My long-term goal is to understand the molecular mechanisms used by HCV to form its membrane-associated replication complexes. I hypothesize that in order to assemble membrane-associated replication complexes, HCV hijacks and redirects the function of components of the host’s vesicular membrane trafficking pathways. I have recently discovered such an interaction between HCV non-structural protein 5A (NS5A) and TBC1D20, a Rab1 GTPase activating protein (GAP) implicated in ER-to-Golgi transport. TBC1D20 depletion impaired HCV replication, with no affect on cell viability. Preliminary experiments reveal that TBC1D20 might also be a GAP for Arf-1, a GTPase implicated in Golgi–to-ER trafficking, suggesting an exciting model wherein NS5A’s interaction with TBC1D20 can subvert both directions of ER-Golgi transport to promote the establishment of the HCV replication complex. This project aims to further determine the role of the NS5A-TBC1D20 interaction in the establishment of the HCV replication complex and to determine the role of Arf1 in HCV replication. Dziedzina nauki natural sciencesbiological sciencesmicrobiologyvirologymedical and health scienceshealth sciencesinfectious diseasesRNA viruseshepatitis Cnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicinehepatologynatural sciencesbiological sciencesgeneticsRNA Słowa kluczowe Arf1 ER Golgi HCV Rab1 non-structural protein 5A (NS5A) vesicular trafficking Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) PEOPLE-2007-4-3.IRG - Marie Curie Action: "International Reintegration Grants" Zaproszenie do składania wniosków FP7-PEOPLE-IRG-2008 Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-IRG - International Re-integration Grants (IRG) Koordynator TEL AVIV UNIVERSITY Wkład UE € 100 000,00 Adres RAMAT AVIV 69978 Tel Aviv Izrael Zobacz na mapie Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Lea Pais (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
