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Environmentally-triggered contraction of the norovirus virion determines diarrheagenic potential

Authors :
Emily W. Helm
Amy M. Peiper
Matthew Phillips
Caroline G. Williams
Michael B. Sherman
Theresa Kelley
Hong Q. Smith
Sorin O. Jacobs
Dhairya Shah
Sarah M. Tatum
Neha Iyer
Marco Grodzki
Joyce C. Morales Aparicio
Elizabeth A. Kennedy
Mikayla S. Manzi
Megan T. Baldridge
Thomas J. Smith
Stephanie M. Karst
Source :
Frontiers in Immunology, Vol 13 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

Noroviruses are the leading cause of severe childhood diarrhea and foodborne disease worldwide. While they are a major cause of disease in all age groups, infections in the very young can be quite severe with annual estimates of 50,000-200,000 fatalities in children under 5 years old. In spite of the remarkable disease burden associated with norovirus infections in people, very little is known about the pathogenic mechanisms underlying norovirus diarrhea, principally because of the lack of tractable small animal models. We recently demonstrated that wild-type neonatal mice are susceptible to murine norovirus (MNV)-induced acute self-resolving diarrhea in a time course mirroring human norovirus disease. Using this robust pathogenesis model system, we demonstrate that virulence is regulated by the responsiveness of the viral capsid to environmental cues that trigger contraction of the VP1 protruding (P) domain onto the particle shell, thus enhancing receptor binding and infectivity. The capacity of a given MNV strain to undergo this contraction positively correlates with infection of cells expressing low abundance of the virus receptor CD300lf, supporting a model whereby virion contraction triggers infection of CD300lflo cell types that are responsible for diarrhea induction. These findings directly link environmentally-influenced biophysical features with norovirus disease severity.

Details

Language :
English
ISSN :
16643224
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
edsdoj.977826bdb7f747619d7e66707745bdfc
Document Type :
article
Full Text :
https://doi.org/10.3389/fimmu.2022.1043746