# Enteric virus-microbiota interactions

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $514,433

## Abstract

Viruses transmitted by the fecal-oral route are among the most common human infections, but little is known
about factors that influence transmission and viral replication in the intestine. The gastrointestinal tract is a
complex environment and enteric viruses encounter a vast microbial community. Intestinal bacteria promote
replication and pathogenesis of enteric viruses in mice, including poliovirus, reovirus, mouse mammary tumor
virus, and norovirus. Thus, unrelated viruses from four families benefit from intestinal bacteria, highlighting the
importance of understanding virus-microbiota interactions. Microbiota promote replication of enteric viruses
through multiple mechanisms, including direct interactions with viral particles that aid attachment and stability,
and indirect modulation of the host innate immune response. Although poliovirus and coxsackievirus B3
(CVB3) are two closely related viruses in the Picornaviridae family, our data suggest that microbiota enhance
their infection through distinct mechanisms. While inhibition of poliovirus replication requires a potent cocktail
of four antibiotics, CVB3 replication is inhibited by much more subtle antibiotic regimens. These results suggest
that CVB3 is more reliant on microbiota than poliovirus and that a specific subset of bacteria may be required
for efficient CVB3 infection. Bacteria in the colon ferment dietary fiber to produce short-chain fatty acids
(SCFAs) including acetate, propionate, and butyrate. SCFAs are among the most abundant molecules in the
distal gastrointestinal tract and influence intestinal metabolism and gene expression in ways that could impact
enteric virus replication. Recently, we determined that a single bacterial metabolite, butyrate, is sufficient to
promote CVB3 replication in microbiota-depleted mice. Our central hypothesis is that bacteria-derived SCFAs
promote enteric virus replication by altering host gene expression and intestinal homeostasis. In this work we
will 1. Examine the specificity of SCFA-mediated effects on enteric virus replication and 2. Examine how
SCFA-mediated changes in host gene expression affect enteric virus replication. Overall, our goal is to use the
power of model viruses to understand mechanisms by which bacteria promote enteric virus infection.

## Key facts

- **NIH application ID:** 10348746
- **Project number:** 5R01AI074668-14
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Julie K Pfeiffer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $514,433
- **Award type:** 5
- **Project period:** 2008-02-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348746

## Citation

> US National Institutes of Health, RePORTER application 10348746, Enteric virus-microbiota interactions (5R01AI074668-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10348746. Licensed CC0.

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