Cytomegalovirus microRNAs facilitate persistent virus infection in salivary glands.

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.