Objective
1. To develop in-vitro translation assays for the design and testing of antiviral drugs against hepatitis c virus (HCV) via a) the characterization of structures important for the initiation of translation and / or replication b) the analysis of interactions between viral-viral and viral-cellular components participating in the translation/replication process c) the synthesis and evaluation of DNA-based antivirals (sODN and ribozymes)
2. To identify immunological determinants relevant for the development of antiHCV vaccines via the use of a) lipopeptide-based immunizations using patients B and T-lymphocytes b) naked-DNA-based immunizations.
A rational basis for the curbing of HCV infection and implementing disease treatment can only be found in a fundamental understanding of the virus, its replication and expression, and the immune responses it elicits. The different expertise required to address those issues in a most productive way, fundamental molecular virology, immunology and organic chemistry, are provided by the multi-center task force participating in the project.
Study of the molecular mechanism of translation initiation and replication will focus on fine mutational analysis of the IRES (Internal Ribosome Entry Site) domain important for the viral translation and replication, as well as RNAprotein and protein-protein interactions involving the 5'NCR (Non Coding Region) and the NS (non-structural) domains, particularly the NS5 domain coding for the viral polymerase. Those will be done using RNA binding assays followed by UV cross-linking experiments and using the yeast derived twohybrid system. Antiviral strategies using antisense oligonucleotides (modified phosphorothioates) targeted at the 5'NCR and hammerhead ribozymes will be evaluated for inhibition of translation and RNAse polymerase inhibition.
Identification of putative immunological determinants relevant for vaccine development will be achieved using B and T cell in-vitro immunization and purified lipopeptides as immunogens. Studies (in a murin model) will also involved the use of expression cassettes for HCV structural genes and direct naked- DNA immunizations. Immunological responses (B and T) will be analyzed.
We will identify and characterize (at the molecular and cellular level) clinical populations displaying specific replicative capacity (i.e enhanced or reduced viremia). Derived cellular and molecular clones will be used to dissect the influence of genomic background on expression level and immunological responses.
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 basic medicine immunology immunisation
- natural sciences biological sciences microbiology virology
- medical and health sciences health sciences infectious diseases RNA viruses hepatitis C
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antivirals
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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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.
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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.
Coordinator
69424 Lyon
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.