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Content archived on 2024-06-18

Subversion of host trafficking machinery by Hepatitis C Virus to promote viral replication

Objective

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.

Fields of science (EuroSciVoc)

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

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FP7-PEOPLE-IRG-2008
See other projects for this call

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IRG - International Re-integration Grants (IRG)

Coordinator

TEL AVIV UNIVERSITY
EU contribution
€ 100 000,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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