Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs: Implications for latency

Eain Murphy, Jiří Vaníček, Harlan Robins, Thomas Shenk, Arnold J. Levine

Research output: Contribution to journalArticle

216 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5453-5458
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number14
DOIs
StatePublished - Apr 8 2008

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Immune evasion
  • Reactivation
  • miRNAs

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