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Journal of Virology, September 2006, p. 8778-8786, Vol. 80, No. 17
0022-538X/06/$08.00+0     doi:10.1128/JVI.00831-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Marek's Disease Virus Encodes MicroRNAs That Map to meq and the Latency-Associated Transcript{dagger}

Joan Burnside,1* Erin Bernberg,1 Amy Anderson,1 Cheng Lu,2 Blake C. Meyers,2 Pamela J. Green,2 Neeta Jain,1 Grace Isaacs,1 and Robin W. Morgan1

Department of Animal and Food Sciences,1 Department of Plant and Soil Sciences, Delaware Biotechnology Institute, University of Delaware, Newark, Delaware 197112

Received 21 April 2006/ Accepted 15 June 2006

MicroRNAs (miRNAs) are a class of small (~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.

* Corresponding author. Mailing address: University of Delaware, Delaware Biotechnology Institute, 15 Innovation Way, Newark, DE 19711. Phone: (302) 831-1345. Fax: (302) 831-3410. E-mail: joan{at}udel.edu.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, September 2006, p. 8778-8786, Vol. 80, No. 17
0022-538X/06/$08.00+0     doi:10.1128/JVI.00831-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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