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Principal Investigator: Dr. Klaus Osterrieder
Contact Information: E-mail: no34@cornell.edu - Phone: 607-253-4045
Sponsor: USDA-NRI
Grant Number: 2005-35204-16276
Title: Immunomodulation by Marek's Disease Virus Glycoprotein C - Implications for Virulence
Annual Direct Cost: $91,685
Project Period: 09/01/05-08/31/08
Marek's disease is a devastating oncogenic viral disease, which affects chickens in the U.S. and worldwide. Despite regular immunizations, re-emerging MD viruses (MDV) break vaccine-induced protection and continue to cause severe problems and economic losses. The first objective of the project is to analyze the relative contributions of different forms of the major antigen, termed glycoprotein C, of Marek's disease virus to disease development. In the second objective, complex partners of glycoprotein C will be identified. The third objective is directed towards a comparison of the function of glycoprotein C in older versus more virulent recent isolates. Importantly, the effect of various forms of the major antigen will be tested in vaccine-challenge experiments using several engineered vaccine viruses.
The objectives of the project are to investigate the role of different forms of the major antigen of Marek's disease virus (MDV), glycoprotein C (gC), in virulence and immune protection. We have discovered that gC is expressed in both membrane-bound and secreted forms and hypothesize that the secreted forms of gC play a major role in the establishment of lytic replication by interfering with the chicken's immune response to infection. The first objective is to analyze the relative contributions of secreted vs. non-secreted gC to virulence and the chicken's immune response. This objective will be achieved by generating and testing mutant virulent viruses that are able to express only either membrane-bound or secreted gC. The second objective is to identify the putative interaction partners of soluble gC by co-immunoprecipitation and mass spectrometry. The third objective is to investigate whether soluble gC plays a more prominent role in newly emerged very virulent plus MDV that are characterized by a more rampant lytic infection. The last objective is to exploit the knowledge generated thus far and in the first objectives to rationally design more efficacious vaccines by removing the ability of vaccine viruses to thwart the immune response by secretion of the viral glycoprotein. Our studies will help in expanding our knowledge on the role of MDV gC ands will hopefully lead to an improvement of the efficacy of vaccination against Marek's disease (MD) by the development of various avirulent MDV strains, which are potentially of advantage for future vaccination strategies.
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