Cytomegalovirus microRNAs facilitate persistent virus infection in salivary glands

Lars Dölken, Astrid Krmpotic, Sheila Kothe, Lee Tuddenham, Mélanie Tanguy, Lisa Marcinowski, Zsolt Ruzsics, Naama Elefant, Yael Altuvia, Hanah Margalit, Ulrich H. Koszinowski, Stipan Jonjic*, Sébastien Pfeffer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Micro (mi)RNAs are small non-coding RNAs that regulate the expression of their targets' messenger RNAs through both translational inhibition and regulation of target RNA stability. Recently, a number of viruses, particularly of the herpesvirus family, have been shown to express their own miRNAs to control both viral and cellular transcripts. Although some targets of viral miRNAs are known, their function in a physiologically relevant infection remains to be elucidated. As such, no in vivo phenotype of a viral miRNA knock-out mutant has been described so far. Here, we report on the first functional phenotype of a miRNA knock-out virus in vivo. During subacute infection of a mutant mouse cytomegalovirus lacking two viral miRNAs, virus production is selectively reduced in salivary glands, an organ essential for virus persistence and horizontal transmission. This phenotype depends on several parameters including viral load and mouse genetic background, and is abolished by combined but not single depletion of natural killer (NK) and CD4+ T cells. Together, our results point towards a miRNA-based immunoevasion mechanism important for long-term virus persistence.

Original languageAmerican English
Article numbere1001150
JournalPLoS Pathogens
Volume6
Issue number10
DOIs
StatePublished - Oct 2010

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