Role of interferon regulatory factor 3 in type I interferon responses in rotavirus-infected dendritic cells and fibroblasts

J Virol. 2007 Mar;81(6):2758-68. doi: 10.1128/JVI.01555-06. Epub 2007 Jan 10.


The main pathway for the induction of type I interferons (IFN) by viruses is through the recognition of viral RNA by cytosolic receptors and the subsequent activation of interferon regulatory factor 3 (IRF-3), which drives IFN-alpha/beta transcription. In addition to their role in inducing an antiviral state, type I IFN also play a role in modulating adaptive immune responses, in part via their effects on dendritic cells (DCs). Many viruses have evolved mechanisms to interfere with type I IFN induction, and one recently reported strategy for achieving this is by targeting IRF-3 for degradation, as shown for rotavirus nonstructural protein 1 (NSP1). It was therefore of interest to investigate whether rotavirus-exposed DCs would produce type I IFN and/or mature in response to the virus. Our results demonstrate that IRF-3 was rapidly degraded in rotavirus-infected mouse embryonic fibroblasts (MEFs) and type I IFN was not detected in these cultures. In contrast, rotavirus induced type I IFN production in myeloid DCs (mDCs), resulting in their activation. Type I IFN induction in response to rotavirus was reduced in mDCs from IRF-3(-/-) mice, indicating that IRF-3 was important for mediating the response. Exposure of mDCs to UV-treated rotavirus induced significantly higher type I IFN levels, suggesting that rotavirus-encoded functions also antagonized the response in DCs. However, in contrast to MEFs, this action was not sufficient to completely abrogate type I IFN induction, consistent with a role for DCs as sentinels for virus infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Cells, Cultured
  • Chlorocebus aethiops
  • Computer Simulation
  • Dendritic Cells / immunology*
  • Dendritic Cells / virology
  • Fibroblasts / immunology*
  • Fibroblasts / virology
  • Fluorescent Antibody Technique, Direct
  • Interferon Regulatory Factor-3 / physiology*
  • Interferon Type I / immunology*
  • L Cells
  • Mice
  • Mice, Inbred C57BL
  • Rotavirus Infections / immunology*
  • Rotavirus Infections / metabolism


  • Interferon Regulatory Factor-3
  • Interferon Type I