title: Marek's disease virus encodes MicroRNAs that map to meq and the latency-associated transcript.
abstract: MicroRNAs (miRNAs) are a class of small (approximately 22-nucleotide) regulatory molecules that block translation or induce degradation of target mRNAs. These have been identified in a wide range of organisms, including viruses. In particular, the oncogenic gammaherpesviruses Kaposi's sarcoma herpesvirus and Epstein-Barr virus encode miRNAs that could potentially regulate either viral or host genes. To determine if Marek's disease virus (MDV), an oncogenic alphaherpesvirus of chickens, encodes miRNAs, we isolated small RNAs from MDV-infected chicken embryo fibroblasts (CEF) and used the 454 Life Sciences sequencing technology to obtain the sequences of 13,679 candidate host and viral small RNAs. Eight miRNAs were found, five of which flank the meq oncogene and three that map to the latency-associated transcript (LAT) region of the genome. The meq gene is unique to pathogenic serotypes of MDV and is transcriptionally active during latency and transformation, and the LAT region of the MDV genome is antisense to the immediate-early gene ICP4. Secondary structure analysis predicted that the regions flanking the miRNAs could form hairpin precursors. Northern blot analysis confirmed expression of all miRNAs in MDV-infected CEF, MDV-induced tumors, and MDV lymphoblastoid cell lines. We propose that the MDV miRNAs function to enable MDV pathogenesis and contribute to MDV-induced transformation of chicken T cells.
authors.affiliation: Department of Animal and Food Sciences, University of Delaware, Newark, 19711, USA. joan@udel.edu
authors.forename: Joan
authors.initials: J
authors.lastname: Burnside
authors.forename: Erin
authors.initials: E
authors.lastname: Bernberg
authors.forename: Amy
authors.initials: A
authors.lastname: Anderson
authors.forename: Cheng
authors.initials: C
authors.lastname: Lu
authors.forename: Blake C
authors.initials: BC
authors.lastname: Meyers
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Green
authors.forename: Neeta
authors.initials: N
authors.lastname: Jain
authors.forename: Grace
authors.initials: G
authors.lastname: Isaacs
authors.forename: Robin W
authors.initials: RW
authors.lastname: Morgan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002642:Chick Embryo; D002874:Chromosome Mapping; D005347:Fibroblasts / Q000821:virology; D008381:Herpesvirus 2, Gallid / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D008380:Marek Disease / Q000821:virology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D017735:Virus Latency / Q000235:genetics / Q000502:physiology*
chemical_list: C100369:Eco-Q protein, Gallid herpesvirus 2; D035683:MicroRNAs; D009856:Oncogene Proteins, Viral; D012367:RNA, Viral; D014764:Viral Proteins