Hypersusceptibility to Vesicular Stomatitis Virus Infection in Dicer1-deficient Mice Is Due to Impaired miR24 and miR93 Expression

Immunity. 2007 Jul;27(1):123-34. doi: 10.1016/j.immuni.2007.05.014. Epub 2007 Jul 5.

Abstract

Dicer is essential for plant, Caenorhabditis elegans, and Drosophila antiviral responses because of its role in generating small interfering RNA (siRNA) from viral genomes. We show that because of impaired miRNA production, mice with a variant Dicer1 allele (Dicer1(d/d)) were more susceptible to vesicular stomatitis virus (VSV) infection. We did not detect VSV genome-derived siRNA in wild-type cells or any alteration of interferon-mediated antiviral responses by Dicer1 deficiency. Rather, we found that host miR24 and miR93 could target viral large protein (L protein) and phosphoprotein (P protein) genes, and a lack of miR24 and miR93 was responsible for increased VSV replication in Dicer1(d/d) cells. Our data suggest that host miRNA can play a role in host interactions with viruses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • DEAD-box RNA Helicases / deficiency*
  • DEAD-box RNA Helicases / genetics*
  • DEAD-box RNA Helicases / physiology
  • Endoribonucleases / deficiency*
  • Endoribonucleases / genetics*
  • Endoribonucleases / physiology
  • Female
  • Genetic Predisposition to Disease*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Rhabdoviridae Infections / genetics*
  • Rhabdoviridae Infections / immunology
  • Rhabdoviridae Infections / metabolism
  • Ribonuclease III
  • Vesicular stomatitis Indiana virus / genetics*

Substances

  • MicroRNAs
  • Endoribonucleases
  • Dicer1 protein, mouse
  • Ribonuclease III
  • DEAD-box RNA Helicases