Avian Herpesvirus MicroRNAs: Roles in Infection, Latency, and Oncogenesis

MicroRNAs are a means of post-transcriptional regulation for viruses that replicate in the nuclei of host cells. In particular, numerous herpesvirus microRNAs have been catalogued, and the elucidation of microRNA functions in herpesviral infections is a current major challenge. MicroRNAs have been described for the avian herpesviruses Marek’s disease virus 1 (MDV1; oncogenic), Marek’s disease virus 2 (MDV2; non-oncogenic), herpesvirus of turkeys (HVT), and infectious laryngotracheitis virus (ILTV).  Phylogenetic relationships among avian herpesvirus microRNAs are not apparent, but the genomic addresses of microRNA clusters are remarkably conserved, with microRNAs mapping to the repeat regions of the genomes. Among MDV1 field isolates with different pathogenicities, microRNAs are highly conserved with the observed variations being in putative promoter regions.  One cluster of MDV1 microRNAs, which lies upstream of the meq gene, appears to be associated with virulence. Several of the avian herpesvirus microRNAs are orthologous to microRNAs in other species.  For example, mdv1-miR-M4 shares its seed sequence with gga-miR-155 and with Kaposi sarcoma herpesvirus (KSHV) kshv-miR-K12.  In addition, mdv2-miR-M21 shares its seed with miR-29b, and hvt-miR-H14 shares its seed sequence with miR-221.  Functional analyses of avian herpesvirus microRNAs include in vitro assays to demonstrate potential function as well as the powerful strategy of using mutants to assess phenotypes experimentally in the natural host.