Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs: implications for latency.
A quantitative algorithm was developed and applied to predict target genes of microRNAs encoded by herpesviruses. Although there is almost no conservation among microRNAs of different herpesvirus subfamilies, a common pattern of regulation emerged. The algorithm predicts that herpes simplex virus 1, human cytomegalovirus, Epstein-Barr virus, and Kaposi's sarcoma-associated herpesvirus all employ microRNAs to suppress expression of their own genes, including their immediate-early genes. In the case of human cytomegalovirus, a virus-coded microRNA, miR-112-1, was predicted to target the viral immediate-early protein 1 mRNA. To test this prediction, mutant viruses were generated that were unable to express the microRNA, or encoded an immediate-early 1 mRNA lacking its target site. Analysis of RNA and protein within infected cells demonstrated that miR-UL112-1 inhibits expression of the major immediate-early protein. We propose that herpesviruses use microRNA-mediated suppression of immediate-early genes as part of their strategy to enter and maintain latency.
Murphy
Eain
E
Simons Center for Systems Biology, Institute for Advanced Study, Princeton, NJ 08540, USA.
Vanícek
Jirí
J
Robins
Harlan
H
Shenk
Thomas
T
Levine
Arnold J
AJ
D000465:Algorithms; D003587:Cytomegalovirus; D015967:Gene Expression Regulation, Viral; D017781:Genes, Immediate-Early / Q000235:genetics*; D006564:Herpesviridae / Q000472:pathogenicity*; D006566:Herpesviridae Infections; D004854:Herpesvirus 4, Human; D019288:Herpesvirus 8, Human; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D018139:Simplexvirus; D017735:Virus Latency / Q000235:genetics*
D035683:MicroRNAs