Objective
HCV infection affects more than 170 million people worldwide and is becoming the first cause of liver transplantation and primary liver cancer in industrialized countries. Whether HCV induces liver cancers through the cirrhosis it causes, or bears intrinsic carcinogenetic properties is debated, and the molecular mechanisms underlying HCV-related hepatocarcinogenesis remain unknown. The hosting laboratory (INSERM U635) has recently shown that quasispecies variants of HCV NS5A protein bear significantly different transactivating properties, according to their amino acid sequence. Such properties could play a role in the early steps of HCV-related hepatocarcinogenesis. We hypothesize that both the core and NS5A transactivating properties play a role in the triggering of early carcinogenetic events in HCV infection and that this role is modulated by the natural variability of these proteins. Intracellular production, even in low amounts, of proteins with strong transactivating properties could interact with cellular mechanisms and have transforming properties on hepatocytes, which may ultimately lead to HCC development.
In this project, we will: 1) characterize the natural genetic variability of core and NS5A variants and its functional impact on their transcription al activities in vitro; 2) study the consequences of HCV protein repertoire expression, ex vivo and in vivo, according to the transcriptional activity of core and NS5A protein variants, and 3) understand the role of transactivation properties carried by HCV proteins in the sequence of HCV-related liver pathogenesis. The originality of our project resides in two key fundamentals: 1) the use of HCV sequences directly cloned from chronically infected patients with well characterized hepatic consequences of HCV infection; and 2) the use of an original experimental animal model based on long-term expression of HCV proteins in the liver of mice transduced by helper-dependant adenoviral vectors.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine oncology liver cancer
- medical and health sciences health sciences infectious diseases RNA viruses hepatitis C
- natural sciences biological sciences biochemistry biomolecules proteins
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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)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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.
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
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2004-MOBILITY-12
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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.
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.
IRG - Marie Curie actions-International re-integration grants
Coordinator
PARIS
France
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.