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.
Max von Pettenkofer-Institute, Ludwig-Maximilians-University Munich, Munich, Germany.
Lars
L
Dölken
Astrid
A
Krmpotic
Sheila
S
Kothe
Lee
L
Tuddenham
Mélanie
M
Tanguy
Lisa
L
Marcinowski
Zsolt
Z
Ruzsics
Naama
N
Elefant
Yael
Y
Altuvia
Hanah
H
Margalit
Ulrich H
UH
Koszinowski
Stipan
S
Jonjic
Sébastien
S
Pfeffer
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