Post-transcriptional regulation of miR-27 in murine cytomegalovirus infection.
In mammals, microRNAs (miRNAs) can play diverse roles in viral infection through their capacity to regulate both host and viral genes. Recent reports have demonstrated that specific miRNAs change in expression level upon infection and can impact viral production and infectivity. It is clear that miRNAs are an integral component of viral-host interactions, and it is likely that both host and virus contain mechanisms to regulate miRNA expression and/or activity. To date, little is known about the mechanisms by which miRNAs are regulated in viral infection. Here we report the rapid down-regulation of miR-27a in multiple mouse cell lines as well as primary macrophages upon infection with the murine cytomegalovirus. Down-regulation of miR-27a occurs independently from two other miRNAs, miR-23a and miR-24, located within the same genomic cluster, and analysis of pri-miRNA levels suggest that regulation occurs post-transcriptionally. miR-27b, a close homolog of miR-27a (20/21 nucleotide identity), also decreases upon infection, and we demonstrate that both miR-27a and miR-27b exert an antiviral function upon over-expression. Drug sensitivity experiments suggest that virus entry is not sufficient to induce the down-regulation of miR-27 and that the mechanism requires synthesis of RNA. Altogether, our findings indicate that miR-27a and miR-27b have antiviral activity against MCMV, and that either the virus or the host encodes molecule(s) for regulating miR-27 accumulation, most likely by inducing the rapid decay of the mature species.
Buck
Amy H
AH
Centre for Immunity, Infection, and Evolution, University of Edinburgh, Edinburgh EH93JT, UK. a.buck@ed.ac.uk
Perot
Jonathan
J
Chisholm
Michael A
MA
Kumar
Diwakar S
DS
Tuddenham
Lee
L
Cognat
Valérie
V
Marcinowski
Lisa
L
Dölken
Lars
L
Pfeffer
Sébastien
S
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D003586:Cytomegalovirus Infections / Q000235:genetics* / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D018146:Muromegalovirus / Q000472:pathogenicity* / Q000502:physiology; D041681:NIH 3T3 Cells; D012323:RNA Processing, Post-Transcriptional
D000998:Antiviral Agents; D017931:DNA Primers; D035683:MicroRNAs; C540674:Mirn27 microRNA, mouse