Objective
Herpes simplex encephalitis (HSE) is a rare disease affecting young children as well as adults due to primary infection with herpes simplex virus-1 (HSV-1). HSV-1 is a nearly ubiquitous virus commonly infecting humans however most do not develop HSE, suggesting that these children possess an underlying genetic susceptibility to HSV-1. In addition, familial forms of HSE have been described, and in our HSE epidemiological study a relatively high incidence of consanguinity was found among HSE patients supporting the notion of a genetic contribution to disease manifestation. Notably, these patients are otherwise healthy and able to mount a normal adaptive immune response to HSV-1, pointing to the likelihood that they harbor an unidentified form of primary immunodeficiency disease affecting their innate immune system. We have recently identified the first two genetic etiologies UNC93B and TLR3 deficiencies in HSE patients validating our hypothesis. Here we propose to use a candidate gene approach to identify other gene(s) involved in HSE by cellular phenotyping and physical mapping. The cellular phenotyping will focus on one of the major components of antiviral innate immunity, namely, the production of and response to interferon-α/β (IFN-α/β). Patients with mutations in UNC93B and TLR3 show reduced IFN production after viral and double-stranded RNA stimulation, revealing this specific UNC93B-TLR3-IFN pathway as relevant to HSE immunity. Hence, HSE patients will be screened for IFN production in response to HSV-1 and Toll-like receptor agonists, and the causative genes identified following a candidate gene approach. In parallel, physical mapping has been initiated following the results of a genome scan of consanguineous families with HSE. The identification of genes involved in HSE will present important biological and medical implications, providing a dissection of immunity to HSV-1 in natural conditions and a rational understanding of HSE pathogenesis.
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
- medical and health sciences basic medicine immunology
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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.
FP7-PEOPLE-2007-2-1-IEF
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.
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
75270 cedex 06 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.