Objective
Increasing evidence suggested that BVDV glycoprotein E2 belongs to the class II viral fusion proteins like flavivirus E and alphavirus E1 protein. In spite of further similarities in entry pathways of BVDV and flavi- and alphaviruses, recently a fundamental difference in the initiation of fusion process was reported.
While flavi- and alphavirus fusion is initiated upon environmental acidification, BVD virions are stabilized by disulfide bridges in the viral glycoproteins. Reduction of these disulfide bridges during invasion facilitates the acid dependent fusion. For closely related Hepatitis C Virus also a considerable acid resistance was observed, suggesting a similar fusion mechanism.
The mechanism of BVDV membrane fusion will be the main goal of this stud y. This requires substantial structural knowledge of the fusion protein. Thus structural analyses on pestiviral glycoproteins will be performed. Disulfide bridges in the E1-E2 heterodimer, purified from virions, will be mapped. In addition the crystal structure of E2 and/or the E1-E2 heterodimer, which is the predominant glycoprotein in the virion, will be determined from glycoproteins that are expressed in Drosophila cells.
A cell-based fusion assay will be established to identify the pestiviral fusion protein by expression of pestiviral glycoproteins at the cell surface. Mutation analysis using reverse genetics will result in the identification of the fusion peptide Understanding of pestiviral fusion mechanism and knowledge of the 3D structure of the pestiviral glycoproteins will have a tremendous impact in understanding the molecular mechanisms of pestivirus entry, and of enveloped viruses in general.
In particular, the differences to fusion mechanisms of flavi- and alphavirus promise an exciting new picture of the class II fusion protein structure/function relationship. The researcher as molecular virologist acquire methods of structural biology and thus strengthen his scientific independence and maturity.
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 health sciences infectious diseases RNA viruses
- engineering and technology materials engineering crystals
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences genetics genomes viral genomes
- agricultural sciences animal and dairy science domestic animals animal husbandry
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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.
FP6-2005-MOBILITY-5
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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.
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.