Protective role of Toll-like Receptor 3-induced type I interferon in murine coronavirus infection of macrophages

Viruses. 2012 May;4(5):901-23. doi: 10.3390/v4050901. Epub 2012 May 24.


Toll-like Receptors (TLRs) sense viral infections and induce production of type I interferons (IFNs), other cytokines, and chemokines. Viral recognition by TLRs and other pattern recognition receptors (PRRs) has been proven to be cell-type specific. Triggering of TLRs with selected ligands can be beneficial against some viral infections. Macrophages are antigen-presenting cells that express TLRs and have a key role in the innate and adaptive immunity against viruses. Coronaviruses (CoVs) are single-stranded, positive-sense RNA viruses that cause acute and chronic infections and can productively infect macrophages. Investigation of the interplay between CoVs and PRRs is in its infancy. We assessed the effect of triggering TLR2, TLR3, TLR4, and TLR7 with selected ligands on the susceptibility of the J774A.1 macrophage cell line to infection with murine coronavirus (mouse hepatitis virus, [MHV]). Stimulation of TLR2, TLR4, or TLR7 did not affect MHV production. In contrast, pre-stimulation of TLR3 with polyinosinic-polycytidylic acid (poly I:C) hindered MHV infection through induction of IFN-β in macrophages. We demonstrate that activation of TLR3 with the synthetic ligand poly I:C mediates antiviral immunity that diminishes (MHV-A59) or suppresses (MHV-JHM, MHV-3) virus production in macrophages.

Keywords: TLR; antiviral state; macrophage; murine coronavirus; poly I:C; type I IFN.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / virology
  • Interferon Type I / biosynthesis
  • Interferon Type I / immunology*
  • Macrophages / immunology*
  • Macrophages / virology*
  • Mice
  • Murine hepatitis virus / growth & development*
  • Murine hepatitis virus / immunology*
  • Poly I-C / immunology
  • Poly I-C / metabolism
  • Toll-Like Receptor 3 / immunology*
  • Toll-Like Receptor 3 / metabolism


  • Interferon Type I
  • Toll-Like Receptor 3
  • Poly I-C