# The Role of Norovirus Interactions with the Epithelial Barrier in Acute Gastroenteritis

> **NIH NIH F30** · UNIVERSITY OF FLORIDA · 2024 · $43,971

## Abstract

Project Summary/Abstract
Norovirus is the leading cause of severe childhood diarrhea around the world and a major cause of acute
gastroenteritis in all age groups. There are no currently approved vaccines or targeted therapeutics for norovirus
infection and very little is known about the pathogenic mechanisms underlying gastroenteritis symptoms. To gain
further understanding of this important virus, murine norovirus has been used as a model system for many years
and has led to significant advances in understanding norovirus biology. However, the absence of symptoms in
immunocompetent adult mice infected with murine norovirus limits the applicability of this model to delineation
of viral mechanisms of disease. We recently discovered that genetically wild-type neonatal mice develop acute,
self-resolving diarrhea when infected with murine norovirus, a disease course that mirrors human norovirus
infection. This novel small animal model of norovirus disease represents a major advance in the norovirus field
since it will enable a complete characterization of viral disease mechanisms and ultimately serve as a platform
to test the efficacy of antiviral compounds in vivo. Using this model, we have observed that murine norovirus
infects subepithelial immune cells in the intestine but not intestinal epithelial cells. The mechanisms by which
murine norovirus transcytoses the epithelial barrier to reach its immune cell targets during symptomatic infection
is unknown and is the focus on Specific Aim 1 of my proposal. Specifically, I will test the hypothesis that murine
norovirus uses two well-established routes for macromolecular transport across the intestinal epithelium,
microfold cells and CX3CR1+ antigen presenting cells that express transepithelial dendrites. Although we did
not observe viral replication in intestinal epithelial cells, there was abundant virus in these cells at the peak of
diarrhea. This finding was surprising given that these cells do not express the virus receptor, nor do they support
viral replication. In Specific Aim 2 of my proposal, I will test the hypothesis that progeny virus complexed with
bile acids are endocytosed by intestinal epithelial cells via engagement of the apical sodium-dependent bile acid
transporter. Overall, my research focuses on understanding norovirus interactions with the intestinal epithelium
because these are undoubtedly key to the induction of diarrhea.

## Key facts

- **NIH application ID:** 10819486
- **Project number:** 5F30AI172364-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Amy Marie Peiper
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $43,971
- **Award type:** 5
- **Project period:** 2023-05-16 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10819486

## Citation

> US National Institutes of Health, RePORTER application 10819486, The Role of Norovirus Interactions with the Epithelial Barrier in Acute Gastroenteritis (5F30AI172364-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10819486. Licensed CC0.

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