Genomics and Marek's disease virus

Marek's disease virus (MDV), a lymphotrophic alphaherpesvirus of chickens, causes a disease that is characterized by tumor formation, immunosuppression and neurological disorders. Recent developments in chicken genomics have been applied to studies of MDV and have advanced our understanding of both the virus and the disease it causes. We have constructed and used microarrays to identify host genes that are up-regulated in chicken embryo fibroblasts infected with MDV as a first step to catalog the host response to infection. An additional level of gene regulation lies at the level of microRNAs (miRNAs). miRNAs are a class of small (approximately 22 nt) regulatory molecules encoded by a wide variety of organisms, including some viruses, that block translation or induce degradation of specific mRNAs. Herpesviruses, which replicate in the nuclei of infected cells, are a particularly important class of viruses that express miRNAs. miRNAs from two of the oncogenic herpesviruses; namely, Kaposi's sarcoma herpesvirus (KSHV) and Epstein-Barr virus (EBV) have been cataloged. We recently identified MDV-encoded miRNAs. One cluster of miRNAs flanks the meq oncogene, and a second cluster maps to the latency associated transcript (LAT) region of the genome. The LATs are encoded anti-sense to the ICP4 immediate early gene, and the meq gene, which is unique to pathogenic serotypes of MDV, is the most likely oncoprotein or co-oncoprotein encoded by MDV. The conservation of these sequences is suggestive of an important role in pathogenesis.