Molecular events and mechanisms of Marek's disease pathogensis

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Marek¿s disease (MD) is one of the most highly oncogenic herpesviruses known. The causative Marek¿s disease virus (MDV) is an alphaherpesvirus encoding more than 100 open reading frames. Molecular mechanisms of oncogenesis of MD are not fully understood. Among the different MDV-encoded genes, Meq gene, which has all the hallmarks of a potent oncogene, is considered to be the most important gene involved in oncogenesis. Although the molecular pathways of Meq-induced oncogenesis are not fully understood, it is believed that its properties of transcriptional activation and interaction with different cellular proteins are important for its oncogenic potential. Major objectives of the present project are to unravel the functions of the Meq using state of the art technologies of BAC mutagenesis, proteomics and analysis of gene expression profiles in Meq-expressing lymphocytes. In addition, we also propose to examine the molecular events and kinetics of viral integration during latency and transformation using Fluorescent in situ hybridisation (FISH). Lastly, using accurate quantitative PCR methods that we have developed, we will examine the virus load in various tissues of vaccinated birds to examine whether the amount of vaccine virus in the vaccinated birds is related to the protection. The project would provide a fundamental understanding not only on the molecular mechanisms of MDV oncogenicity, but also on the multitude of factors associated with neoplasia in general.