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.
Dölken
Lars
L
Max von Pettenkofer-Institute, Ludwig-Maximilians-University Munich, Munich, Germany.
Krmpotic
Astrid
A
Kothe
Sheila
S
Tuddenham
Lee
L
Tanguy
Mélanie
M
Marcinowski
Lisa
L
Ruzsics
Zsolt
Z
Elefant
Naama
N
Altuvia
Yael
Y
Margalit
Hanah
H
Koszinowski
Ulrich H
UH
Jonjic
Stipan
S
Pfeffer
Sébastien
S
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D055786:Gene Knockout Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D030781:Organisms, Genetically Modified; D012367:RNA, Viral / Q000235:genetics / Q000502:physiology; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D014613:Vaccines, Attenuated / Q000235:genetics; D019562:Viral Load / Q000235:genetics
D035683:MicroRNAs; D012367:RNA, Viral; D014613:Vaccines, Attenuated