# Suppression of Enteric Norovirus Infection by Microbiota-Regulated Bile Acids

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2021 · $537,428

## Abstract

Project Summary
An immense population of microorganisms, collectively referred to as the microbiota, colonizes the mammalian
host. In addition to bacteria, nonpathogenic and pathogenic viruses enter hosts via the gastrointestinal tract. Of
particular clinical importance are noroviruses, which are responsible for ~20% of pediatric diarrheal cases
globally, are the leading cause of severe childhood diarrhea, and are associated with devastating infections in
immunocompromised hosts. Considering that all enteric viruses encounter the intestinal microbiota as they
traverse the mammalian gastrointestinal tract, it is imperative to consider how virus-bacteria interactions may
impact the outcome of viral infections. Indeed, over the past seven years it has become well-established that
commensal bacteria profoundly regulate enteric virus infections. The focus of this application will be the influence
of the intestinal microbiota on noroviruses, using murine norovirus as a model system. We have recently
discovered that commensal bacteria suppress norovirus infection of the proximal region of the gastrointestinal
tract, and that this inhibition is entirely dependent on type III interferon signaling. Furthermore, we can rescue
inhibition in bacteria-depleted mice by supplementing their chow with a single bile acid. These data lead to our
working model that bacterially metabolized bile acids prime type III interferon induction in the proximal gut,
thereby inhibiting norovirus infection. The main objective of this proposal is to delineate the underlying
mechanism for bacterial suppression of norovirus infection in the proximal gut. To this end, we will test the
specific hypothesis that primary bile acids suppress murine norovirus infection of the proximal gut; determine
whether primary bile acids prime type III interferon induction in vivo; and uncover the molecular mechanism by
which primary bile acids prime type III interferon production. Our findings could inform development of novel
interventions based on prebiotics or applied metabolomics.

## Key facts

- **NIH application ID:** 10061535
- **Project number:** 5R01AI141478-03
- **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:** $537,428
- **Award type:** 5
- **Project period:** 2018-11-25 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10061535

## Citation

> US National Institutes of Health, RePORTER application 10061535, Suppression of Enteric Norovirus Infection by Microbiota-Regulated Bile Acids (5R01AI141478-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10061535. Licensed CC0.

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