Cytomegalovirus miRNAs target secretory pathway genes to facilitate formation of the virion assembly compartment and reduce cytokine secretion

Lauren M. Hook, Finn Grey, Robert Grabski, Rebecca Tirabassi, Tracy Doyle, Meaghan Hancock, Igor Landais, Sophia Jeng, Shannon McWeeney, William Britt, Jay A. Nelson

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Herpesviruses, including human cytomegalovirus (HCMV), encode multiple microRNAs (miRNA) whose targets are just being uncovered. Moreover, miRNA function during the virus life cycle is relatively unknown. We find that HCMV miRs UL112-1, US5-1, and US5-2 target multiple components of the host secretory pathway, including VAMP3, RAB5C, RAB11A, SNAP23, and CDC42. A HCMV miR UL112-1, US5-1, and US5-2 triple mutant displayed aberrant morphogenesis of the virion assembly compartment (VAC), increased secretion of noninfectious particles, and increased IL-6 release from infected cells. Ectopic expression of miRs UL112-1, US5-1, and US5-2 or siRNAs directed against RAB5C, RAB11A, SNAP23, and CDC42 caused the loss of Golgi stacks with reorganization into structures that resemble the VAC and a decrease in cytokine release. These observations indicate that multiple HCMV miRNAs coordinately regulate reorganization of the secretory pathway to control cytokine secretion and facilitate formation of the VAC for efficient infectious virus production.

Original languageEnglish (US)
Pages (from-to)363-373
Number of pages11
JournalCell Host and Microbe
Volume15
Issue number3
DOIs
StatePublished - Mar 12 2014

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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