JVI Accepts, published online ahead of print on 4 November 2009

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Walz, N. Articles by Grundhoff, A. PubMed PubMed Citation Articles by Walz, N. Articles by Grundhoff, A.

 Previous Article  |  Next Article 

J. Virol. doi:10.1128/JVI.01302-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A Global Analysis of Evolutionary Conservation among Known and Predicted Gammaherpesvirus miRNAs

Nicole Walz, Thomas Christalla, Uwe Tessmer, and Adam Grundhoff^*

Heinrich-Pette-Institute for experimental Virology and Immunology, Martinistrasse 52, D-20251 Hamburg, Germany

^* To whom correspondence should be addressed. Email: adam.grundhoff{at}hpi.uni-hamburg.de.

microRNAs (miRNAs) are small, non-coding RNAs which post-transcriptionally regulate gene expression. The current release of the miRNA registry lists 16 viruses which encode a total of 146 miRNA hairpins. Strikingly, 139 of these are encoded by members of the herpesvirus family, suggesting an important role for miRNAs in the herpesvirus lifecycle. However, with the exception of 7 miRNA hairpins known to be shared by Epstein-Barr virus (EBV) and the closely related rhesus lymphocryptovirus (rLCV), the known herpesvirus miRNAs show little evidence of evolutionary conservation. We have performed a global analysis of miRNA conservation among gammaherpesviruses which is not limited to family members known to encode miRNAs, but also includes those which have not been previously analyzed. For this purpose, we have performed a computational prediction of miRNA candidates of all fully sequenced gammaherpesvirus genomes, followed by sequence/structure alignments. Our results indicate that gammaherpesvirus miRNA conservation is limited to two pairs of viral genomes: One is the already known case of EBV and rLCV. These viruses, however, share significantly more miRNAs than previously thought, as we identified and experimentally verified 10 novel conserved as well as 7 novel non-conserved rLCV pre-miRNA hairpins. The second case consists of rhesus rhadinovirus (RRV), which is predicted to share at least 9 pre-miRNAs with the closely related Japanese Macaque Herpesvirus (JMHV). Although several other gammaherpesviruses are predicted to encode large numbers of clustered miRNAs at conserved genomic loci, no further examples of evolutionary conserved miRNA sequences were found.