MDA-5 recognition of a murine norovirus

PLoS Pathog. 2008 Jul 18;4(7):e1000108. doi: 10.1371/journal.ppat.1000108.


Noroviruses are important human pathogens responsible for most cases of viral epidemic gastroenteritis worldwide. Murine norovirus-1 (MNV-1) is one of several murine noroviruses isolated from research mouse facilities and has been used as a model of human norovirus infection. MNV-1 infection has been shown to require components of innate and adaptive immunity for clearance; however, the initial host protein that recognizes MNV-1 infection is unknown. Because noroviruses are RNA viruses, we investigated whether MDA5 and TLR3, cellular sensors that recognize dsRNA, are important for the host response to MNV-1. We demonstrate that MDA5-/- dendritic cells(DC) have a defect in cytokine response to MNV-1. In addition, MNV-1 replicates to higher levels in MDA5-/- DCs as well as in MDA5-/- mice in vivo. Interestingly, TLR3-/- DCs do not have a defect in vitro, but TLR3-/- mice have a slight increase in viral titers. This is the first demonstration of an innate immune sensor for norovirus and shows that MDA5 is required for the control of MNV-1 infection. Knowledge of the host response to MNV-1 may provide keys for prevention and treatment of the human disease.

Publication types

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

MeSH terms

  • Animals
  • Bone Marrow Cells
  • Caliciviridae Infections / immunology
  • Caliciviridae Infections / virology*
  • Cell Line
  • DEAD-box RNA Helicases / physiology*
  • Dendritic Cells / virology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gastroenteritis / immunology
  • Gastroenteritis / virology*
  • Immunity, Innate
  • Interferon-Induced Helicase, IFIH1
  • Male
  • Mice
  • Mice, Knockout
  • Norovirus / physiology*
  • RNA, Viral
  • Toll-Like Receptor 3 / physiology
  • Virus Replication


  • RNA, Viral
  • TLR3 protein, mouse
  • Toll-Like Receptor 3
  • Ifih1 protein, mouse
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1