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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Autores principales: Stephen A McCartney, Larissa B Thackray, Leonid Gitlin, Susan Gilfillan, Herbert W Virgin, Marco Colonna
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Publicado: Public Library of Science (PLoS) 2008
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Acceso en línea:https://doaj.org/article/bb03f94d78a9418b89401e29e4d4c8d5
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spelling oai:doaj.org-article:bb03f94d78a9418b89401e29e4d4c8d52021-11-25T05:46:30ZMDA-5 recognition of a murine norovirus.1553-73661553-737410.1371/journal.ppat.1000108https://doaj.org/article/bb03f94d78a9418b89401e29e4d4c8d52008-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18636103/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Noroviruses 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.Stephen A McCartneyLarissa B ThackrayLeonid GitlinSusan GilfillanHerbert W VirginMarco ColonnaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 4, Iss 7, p e1000108 (2008)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Stephen A McCartney
Larissa B Thackray
Leonid Gitlin
Susan Gilfillan
Herbert W Virgin
Marco Colonna
MDA-5 recognition of a murine norovirus.
description 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.
format article
author Stephen A McCartney
Larissa B Thackray
Leonid Gitlin
Susan Gilfillan
Herbert W Virgin
Marco Colonna
author_facet Stephen A McCartney
Larissa B Thackray
Leonid Gitlin
Susan Gilfillan
Herbert W Virgin
Marco Colonna
author_sort Stephen A McCartney
title MDA-5 recognition of a murine norovirus.
title_short MDA-5 recognition of a murine norovirus.
title_full MDA-5 recognition of a murine norovirus.
title_fullStr MDA-5 recognition of a murine norovirus.
title_full_unstemmed MDA-5 recognition of a murine norovirus.
title_sort mda-5 recognition of a murine norovirus.
publisher Public Library of Science (PLoS)
publishDate 2008
url https://doaj.org/article/bb03f94d78a9418b89401e29e4d4c8d5
work_keys_str_mv AT stephenamccartney mda5recognitionofamurinenorovirus
AT larissabthackray mda5recognitionofamurinenorovirus
AT leonidgitlin mda5recognitionofamurinenorovirus
AT susangilfillan mda5recognitionofamurinenorovirus
AT herbertwvirgin mda5recognitionofamurinenorovirus
AT marcocolonna mda5recognitionofamurinenorovirus
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