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Reverse Genetics Mediated Recovery of Infectious Murine Norovirus
Published on: June 24, 2012
Norovirus infection causes acute self-resolving diarrhea in wild-type neonatal mice
Alexa N Roth1, Emily W Helm1, Carmen Mirabelli2
1Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA.
Abstract:
Human noroviruses are the leading cause of severe childhood diarrhea worldwide, yet we know little about their pathogenic mechanisms. Murine noroviruses cause diarrhea in interferon-deficient adult mice but these hosts also develop systemic pathology and lethality, reducing confidence in the translatability of findings to human norovirus disease. Herein we report that a murine norovirus causes self-resolving diarrhea in the absence of systemic disease in wild-type neonatal mice, thus mirroring the key features of human norovirus disease and representing a norovirus small animal disease model in wild-type mice. Intriguingly, lymphocytes are critical for controlling acute norovirus replication while simultaneously contributing to disease severity, likely reflecting their dual role as targets of viral infection and key components of the host response.
Insights
A new murine norovirus model in neonatal mice mimics human norovirus disease, aiding research into childhood diarrhea. Lymphocytes are key to controlling viral replication but also worsen disease severity.
Area of Science:
- Virology
- Immunology
- Pediatric Gastroenterology
Background:
- Human noroviruses are a primary cause of severe childhood diarrhea globally.
- Current murine norovirus models in adult mice exhibit systemic pathology, limiting translatability to human disease.
Purpose of the Study:
- To establish a small animal model that accurately reflects human norovirus disease characteristics.
- To investigate the role of the host immune response in norovirus pathogenesis.
Main Methods:
- Utilized a murine norovirus in wild-type neonatal mice.
- Observed disease progression, focusing on diarrhea and systemic pathology.
- Assessed the role of lymphocytes in viral control and disease severity.
Main Results:
- A murine norovirus caused self-resolving diarrhea in neonatal mice without systemic disease.
- This model effectively mirrors key features of human norovirus illness.
- Lymphocytes were found to be crucial for controlling viral replication but also contributed to disease severity.
Conclusions:
- The developed model provides a valuable tool for studying human norovirus pathogenesis in a relevant host.
- Lymphocytes play a dual role in norovirus infection, acting as both targets and effectors in the host response.

