MDA-5 Recognition of a Murine Norovirus

PLoS Pathogens

Larissa B. Thackray¹  Herbert W. Virgin IV¹  Leonid Gitlin¹  Susan Gilfillan¹  Marco Colonna¹  Stephen A. McCartney¹ 

[1] Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America

关键词: Norovirus;    Viral replication;    Cytokines;    Gastrointestinal tract;    Calicivirus infection;    Toll-like receptors;    Ribonucleases;    Interferons;   

DOI  :  10.1371/journal.ppat.1000108

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY