Functional analysis of novel microRNAs encoded by avian herpesviruses

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Marek's disease (MD) is a common disease of chickens involving paralysis and commonly death from the growth of highly malignant T lymphomas (cancers of white blood cells). MD is caused by a transmissible agent, Marek's disease virus (MDV). MDV is very contagious and is a major threat to the poultry industry worldwide. Presently, it is controlled by vaccination, and nearly 22 billion vaccine doses a year are used in an attempt to control the disease. Despite this, there is a continuous evolution of the virus towards greater virulence necessitating the introduction of new vaccines at regular intervals of 8-10 years when the previous generation of vaccine becomes ineffective. The mechanisms by which the virus gains virulence and produces tumours remain very poorly understood. During the last 2 years, with the financial support from the BBSRC, we have been examining the role of novel regulatory molecules called microRNAs (small 22-nucleotide long RNA molecules) encoded by the virus and the host in inducing MD. As part of this grant, we have identified several novel microRNAs in the genome of the 3 members of the genus Mardivirus. Preliminary studies have indicated that these tiny molecules are produced at very high levels in MDV-induced cancer cells and their deletion from the virus genome affected their ability to produce tumours. In this proposal, which is aimed to build on the findings of our work, we want to continue our research to identify the molecules targeted by the virus-encoded miRNAs and examine the effect of deleting these microRNAs from the genomes of these viruses.