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Interaction of Marek's disease virus Meq protein and chicken CtBP in cell transformation and the pathogenesis of Marek's disease

ReferenceBB/C514731/1
Principal Investigator / Supervisor Professor Martin Allday
Co-Investigators /
Co-Supervisors
Institution Imperial College London
DepartmentDiv of Investigative Science
Funding typeResearch
Value (£) 220,522
StatusCompleted
TypeResearch Grant
Start date 01/06/2005
End date 31/05/2008
Duration36 months

Abstract

We have previously shown that Epstein-Barr virus (EBV) nuclear antigens EBNA3A and EBNA3C can bind to the cellular protein CtBP. This factor is a highly conserved co-repressor of transcription involved in many diverse processes including cell cycle regulation and apoptosis. The ability of EBNA3A and EBNA3C to bind CtBP correlates with their ability to repress transcription and act as oncogenes. Recently, we identified a potential CtBP-binding motif (PLDLS) in the Meq nuclear protein encoded by Marek¿s disease virus (MDV). MDV is an alpha-herpesvirus of chickens that like EBV can induce malignant lymphoproliferative disease. The T cell hyperplasia it produces is responsible for many of the symptoms of the fatal disease of chickens known as Marek¿s disease (MD). By constructing mutants of Meq in a bacterial artificial chromosome clone of MDV, we showed that this interaction between Meq and CtBP is essential for MDV-associated oncogenicity in chickens (although it is unnecessary for MDV replication). We now propose to discover the precise molecular mechanisms responsible for this striking phenotype. Also because the CtBP-binding mutant viruses appear to be completely non-pathogenic, their utility in the development of a new vaccine will be explored. Joint with BB/C518265/1

Summary

unavailable
Committee Closed Committee - Animal Sciences (AS)
Research TopicsAnimal Health, Immunology, Microbiology
Research PriorityX – Research Priority information not available
Research Initiative X - not in an Initiative
Funding SchemeX – not Funded via a specific Funding Scheme
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