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 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.
McCartney
Stephen A
SA
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Thackray
Larissa B
LB
Gitlin
Leonid
L
Gilfillan
Susan
S
Virgin
Herbert W
HW
Virgin Iv
Herbert W
HW
Colonna
Marco
M
D000818:Animals; D001854:Bone Marrow Cells; D017250:Caliciviridae Infections / Q000276:immunology / Q000821:virology*; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000502:physiology*; D003713:Dendritic Cells / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005759:Gastroenteritis / Q000276:immunology / Q000821:virology*; D007113:Immunity, Innate; D000072640:Interferon-Induced Helicase, IFIH1; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D029322:Norovirus / Q000502:physiology*; D012367:RNA, Viral; D051196:Toll-Like Receptor 3 / Q000502:physiology; D014779:Virus Replication
D012367:RNA, Viral; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; C510592:Ifih1 protein, mouse; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1