# Elucidation of Pathogenic Mechanisms underlying Norovirus Diarrhea

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2021 · $603,957

## Abstract

Project Summary
Noroviruses are a major cause of acute gastroenteritis and the leading cause of severe childhood
diarrhea globally. Our discovery of murine norovirus (MNV) in 2003 accelerated progress in the
field by providing a small animal model and enabling further understanding of the pathogenesis
of these enteric viruses. Yet a major limitation of this model system is that wild-type laboratory
mice have not been shown to develop overt disease when infected with MNV, in contrast to human
norovirus which is symptomatic in immunocompetent hosts. This limits the field’s ability to
elucidate norovirus-induced events responsible for disease. It should be noted, however, that all
virulence studies of MNV performed to date have used adult mice. Considering that human
norovirus infections are more severe in younger hosts, we hypothesized that young mice would
likewise be susceptible to MNV disease. We have generated exciting data confirming that oral
MNV infection causes acute self-resolving diarrhea in neonatal pups, a transformative discovery
for the norovirus field. Gastrointestinal disease severity is regulated by viral genetic determinants
and is associated with pathological changes to the intestinal epithelium although the main targets
of infection are intestinal immune cells. We propose to use this novel system to test our working
model that infection of intestinal immune cells leads to disruption of the epithelium and
consequent diarrhea. Our main objectives are to elucidate the viral determinants of diarrhea,
define the key immune cell targets of infection, and probe the interactions of the virus with the
intestinal epithelium. The integration of these aims will enable us to map key virus-host
interactions responsible for intestinal disease.

## Key facts

- **NIH application ID:** 10277083
- **Project number:** 1R01AI162970-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Stephanie M Karst
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $603,957
- **Award type:** 1
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10277083

## Citation

> US National Institutes of Health, RePORTER application 10277083, Elucidation of Pathogenic Mechanisms underlying Norovirus Diarrhea (1R01AI162970-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10277083. Licensed CC0.

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