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Journal of Virology, December 2008, p. 12213-12220, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01722-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Sequence Conservation and Differential Expression of Marek's Disease Virus MicroRNAs{triangledown}

Robin Morgan,1* Amy Anderson,1 Erin Bernberg,1 Sachin Kamboj,3 Emily Huang,1 Grace Lagasse,1 Grace Isaacs,1 Mark Parcells,1 Blake C. Meyers,2 Pamela J. Green,2 and Joan Burnside1*

Department of Animal and Food Sciences,1 Department of Plant and Soil Sciences,2 Department of Computer and Information Sciences, Delaware Biotechnology Institute, University of Delaware, Newark, Delaware 197113

Received 13 August 2008/ Accepted 30 September 2008

Marek's disease virus (MDV), a herpesvirus that causes a lymphoproliferative disorder in chickens, encodes a number of microRNAs derived primarily from two locations in the MDV genome. One cluster of microRNA genes flanks the meq oncogene, and a second cluster is found within the latency-associated transcript (LAT) region. The sequences of MDV microRNAs from a collection of field and reference strains with various levels of virulence were compared and found to be highly conserved. However, microRNAs from the meq cluster were detected at higher levels in lymphomas caused by a form of the virus designated very virulent plus (vv+; strain 615K, also known as T. King) than in those caused by a less virulent (very virulent [vv]) form (RB1B). For example, levels of mdv1-miR-M4, which shares a seed sequence with miR-155, a microRNA implicated in B-cell lymphoma, were threefold higher and levels of mdv1-miR-M2*/3p were more than sixfold higher in vv+ MDV-induced tumors than in vv MDV-induced tumors. In contrast, levels of the microRNAs from the LAT cluster were equivalent in tumors produced by vv and vv+ strains. Additionally, mdv1-miR-M4 is the MDV microRNA most highly expressed in tumors, where it accounts for 72% of all MDV microRNAs, as determined by deep sequencing. These data suggest that the meq cluster microRNAs play an important role in the pathogenicity of MDV.

* Corresponding author. Mailing address: Delaware Biotechnology Institute, University of Delaware, 15 Innovation Way, Newark, DE 19711. Phone: (302) 831-1345. Fax: (302) 831-4054. E-mail for Joan Burnside: joan{at}udel.edu. E-mail for Robin Morgan: morgan{at}udel.edu

{triangledown} Published ahead of print on 8 October 2008.

Journal of Virology, December 2008, p. 12213-12220, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01722-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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