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Journal of Virology, October 2009, p. 10684-10693, Vol. 83, No. 20
0022-538X/09/$08.00+0     doi:10.1128/JVI.01292-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Analysis of Human Cytomegalovirus-Encoded MicroRNA Activity during Infection{triangledown} ,{dagger}

Noam Stern-Ginossar,1 Niveen Saleh,2 Miri D. Goldberg,2 Mark Prichard,3 Dana G. Wolf,2,§ and Ofer Mandelboim1*,§

Lautenberg Center for General and Tumor Immunology, The Hebrew University, IMRIC, Hadassah Medical School,1 Department of Clinical Microbiology and Infectious Diseases, Hadassah University Hospital, Jerusalem, Israel,2 Department of Pediatrics, University of Alabama, Birmingham, Alabama 352333

Received 24 June 2009/ Accepted 28 July 2009

MicroRNAs (miRNAs) are expressed in a wide variety of organisms, ranging from plants to animals, and are key posttranscriptional regulators of gene expression. Virally encoded miRNAs are unique in that they could potentially target both viral and host genes. Indeed, we have previously demonstrated that a human cytomegalovirus (HCMV)-encoded miRNA, miR-UL112, downregulates the expression of a host immune gene, MICB. Remarkably, it was shown that the same miRNA also downregulates immediate-early viral genes and that its ectopic expression resulted in reduced viral replication and viral titers. The targets for most of the viral miRNAs, and hence their functions, are still unknown. Here we demonstrate that miR-UL112 also targets the UL114 gene, and we present evidence that the reduction of UL114 by miR-UL112 reduces its activity as uracil DNA glycosylase but only minimally affects virus growth. In addition, we show that two additional HCMV-encoded miRNAs, miR-US25-1 and miR-US25-2, reduce the viral replication and DNA synthesis not only of HCMV but also of other viruses, suggesting that these two miRNAs target cellular genes that are essential for virus growth. Thus, we suggest that in addition to miR-UL112, two additional HCMV miRNAs control the life cycle of the virus.

* Corresponding author. Mailing address: Lautenberg Center for General and Tumor Immunology, The Hebrew University, IMRIC, Hadassah Medical School, Jerusalem, Israel. Phone: 972-2-6757515. Fax: 972-2-6424653. E-mail: oferm{at}ekmd.huji.ac.il

{triangledown} Published ahead of print on 5 August 2009.

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

§ D.G.W. and O.M. contributed equally to this work.

Journal of Virology, October 2009, p. 10684-10693, Vol. 83, No. 20
0022-538X/09/$08.00+0     doi:10.1128/JVI.01292-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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