MDA-5 recognition of a murine norovirus

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 bee...

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Bibliographic Details
Published in:PLoS pathogens 2008-07, Vol.4 (7), p.e1000108-e1000108
Main Authors: McCartney, Stephen A, Thackray, Larissa B, Gitlin, Leonid, Gilfillan, Susan, Virgin, Herbert W, Virgin Iv, Herbert W, Colonna, Marco
Format: Article
Language:English
Subjects:
Animals
Bone Marrow Cells
Caliciviridae Infections - immunology
Caliciviridae Infections - virology
Causes of
Cell Line
Cytokines
DEAD-box RNA Helicases - physiology
Dendritic Cells - virology
Enzyme-Linked Immunosorbent Assay
Female
Gastroenteritis
Gastroenteritis - immunology
Gastroenteritis - virology
Health aspects
Immune system
Immunity, Innate
Immunology/Immunity to Infections
Immunology/Innate Immunity
Infectious Diseases/Viral Infections
Interferon-Induced Helicase, IFIH1
Male
Mice
Mice, Knockout
Microbiology
Norovirus
Norovirus - physiology
Norwalk virus
Physiological aspects
Proteins
RNA, Viral
Toll-Like Receptor 3 - physiology
Viral infections
Virus Replication
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1000108