We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
MDA-5 Recognition of a Murine Norovirus.
- Authors
McCartney, Stephen A.; Thackray, Larissa B.; Gitlin, Leonid; Gilfillan, Susan; Virgin IV, Herbert W.; Colonna, Marcoz
- Abstract
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.
- Subjects
NOROVIRUSES; IMMUNE system; DENDRITIC cells; RNA viruses; PATHOGENIC microorganisms
- Publication
PLoS Pathogens, 2008, Vol 4, Issue 7, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1000108