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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

Reference	BB/C518265/1
Principal Investigator / Supervisor	Professor Venugopal Nair
Co-Investigators / Co-Supervisors	Professor Martin Allday
Institution	The Pirbright Institute
Department	Div of Immunology Compton
Funding type	Research
Value (£)	251,394
Status	Completed
Type	Research Grant
Start date	01/12/2005
End date	31/03/2009
Duration	40 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/C514731/1

Summary

unavailable

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

Associated awards:

BB/C514731/1 Interaction of Marek's disease virus Meq protein and chicken CtBP in cell transformation and the pathogenesis of Marek's disease

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