Objective
-To determine the role of herpesvirus glycoproteins in viral neurotropism.
-To examine the role of other viral proteins involved in penetration, propagation or persistence in the nervous system.
-To undertake a structural study of selected herpes proteins involved in neurotropism.
We propose to elucidate which viral functions are necessary for alphaherpesviruses to penetrate and propagate in the nervous system. We plan to address this question both in vitro, in polarised cells and in primary cultures of neurons, and in vivo in suitable animal models, using appropriate mutants in which the gene of interest will be deleted. Our first objective will be to analyse the role of the external proteins of HSV1, PrV and VZV virons in the viral neurotropism. Our previous work has led to a better understanding on the role of five of the eleven herpes glycoproteins. We now plan to examine the role of the six other glycoproteins, by comparing the neurotropism of deletion mutants with that of wild type or rescued viruses, after intranasal inoculation of mice.
In addition to envelope glycoproteins, we will also examine other viral proteins which could play a role in neurotropism. Proteins UL 3.5 and UL 20 of PrV have been demonstrated to be involved in the egress of virions from the nucleus to the cytoplasmic membrane. Since this process is poorly understood in neurons but is important for transneuronal spread, respective mutant viruses will be analysed in vitro and in vivo. Protein IE63 of VZV is expressed in large amount during latency in neurons of rat and man. It is also expressed during productive infection in cell cultures, in the skin during zoster and in sensory ganglia during reactivation. Hence its exact role is unclear. Using transient expression assays, it has been shown that IE63 inhibits indirectly the expression of "immediate early" (IE) genes by decreasing the activity of an activating protein. This protein probably plays an important role in VZV latency and reactivation and its exact role will be investigated.
Finally, we propose to undertake a structural study of selected herpes proteins which have been involved in specific interactions with the host cell. Here we propose to study the major attachment proteins of PrV, gB and gC, and protein IE63 of VZV. If enough protein in its native configuration can be obtained from suitable expression systems, crystallisation will be attempted.
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.
- natural sciences biological sciences neurobiology
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences health sciences infectious diseases DNA viruses
You need to log in or register to use this function
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.
Data not available
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
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
91198 GIF SUR YVETTE
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.