Immunology of Marek's disease virus infection in chickens

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Animal infectious diseases are of great importance to human and animal health. Moreover, these diseases impose significant economic losses to the food animal industry. Marek's disease (MD) is a disease of chickens caused by a virus, Marek's disease virus or MDV, and marked by formation of lymphomas, or cancer of immune system cells. This disease provides a unique model for studying the role of immune system and the genes, which control the immune mediators, in conferring resistance to disease. Resistance to MD is genetically controlled and several genes have been shown to play a role in immunity. Moreover, this is probably the first cancer against which a commercial vaccine became available. However, little is known about the mechanisms through which vaccines can prevent disease. Also, the vaccine is not effective at eliminating or reducing virus shedding from the infected birds. Virus shedding predisposes other birds to infection and, more importantly, creates an opportunity for the virus to enhance its disease-causing capacity. The proposed program is intended to investigate, at the molecular and cellular levels, induction and regulation of chicken immune response against MDV infection. Cells of the immune system, such as T cells, have been shown to be important in protection against viral insults. The objectives of this program are to: 1- identify the molecular determinants of MDV recognized by T cells leading to protection against disease, 2- examine T cell responses to the virus in feathers and lungs, which are critical tissues for MDV life cycle, 3- understand the events that occur in feathers rendering T cells unable to eliminate the virus in feathers. It is expected that findings of the proposed studies will expand our understanding of host-pathogen interactions and will also layout the foundation for future studies aimed at designing rational vaccines against MD, which are more effective at control of virus shedding.