Emerging roles of chicken and viral microRNAs in avian disease

ABSTRACT: BACKGROUND: MicroRNAs are short RNAs (~22 nt) expressed by plants, animals and viruses that regulate gene expression post-transcriptionally, and their importance is highlighted by distinct patterns of expression in many physiological processes, including development, hematopoeisis, stress resistance, and disease. Our group has characterized the microRNAs encoded by the avian herpesviruses; namely, oncogenic Marek’s disease (MD) virus (MDV1), non-oncogenic MDV (MDV2) herpesvirus of turkeys (HVT), and infectious laryngotracheitis virus (ILTV). METHODS: MicroRNAs encoded by the avian herpesviruses were identified using next generation sequencing technologies (454, Illumina). RESULTS: The microRNAs of each the avian herpesviruses have unique sequences, but the genomic locations are similar, in that the microRNAs tend to be clustered in the rapidly evolving repeat regions of the viral genomes. For a given viral species the microRNA sequence is highly conserved in different strains with the exception of a virulence-associated polymorphism in the putative promoter of the MDV1 microRNAs upstream of the meq oncogene. These microRNAs are relatively highly expressed in tumors produced by very virulent MDV1 isolates compared to tumors produced by less virulent strains. MDV1 and HVT encode homologs of the host microRNA, miR-221, which targets a gene important in cell cycle regulation. MDV1 encodes a microRNA (mdv1-miR-M4) that shares a seed sequence with miR-155, a microRNA important in immune function. Mdv-miR-M4 is highly expressed in MDV induced tumors, while miR-155 is present at very low levels. CONCLUSIONS: MicroRNAs are highly conserved among different field strains of MDV1, and they are expressed in lytic and latent infections and in MDV1-derived tumors. This suggests that these small molecules are very important to the virus, and roles in immune evasion, anti-apoptosis, or proliferation are likely.