# Modulation of host metabolism by a persistent enteric virus

> **NIH NIH F31** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $37,019

## Abstract

Project Summary
The bacterial microbiome of the mammalian gut has an indispensable role in a number of processes important
to host survival, including fermentation, intestinal development, immune instruction and, through soluble
mediators, the development of other organ systems. Dysbiosis has been linked to a number of pathologies,
including metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Much less is known about the
influence of the viral population of the mammalian gut, and no existing links between the enteric virome and
host metabolic function have been shown. Norovirus is small +RNA virus that can establish persistent enteric
infections in mice and humans and serves as a model of virus-host interactions at the intestinal mucosa.
Previous experiments from our lab established that Murine Norovirus (MNV) infection can recapitulate some of
the key functions of the commensal flora in microbiota-depleted mice. Remarkably, these effects were spread
throughout the intestine and were not limited to the MNV replication niche in the ileum. Because MNV is able to
influence intestinal physiology indirectly, we hypothesized that its presence can also have an effect on other
organs such as the liver, in a manner similar to gut bacteria. We found that MNV-infected mice have an altered
metabolic profile and a distinct transcriptional signature in the liver, both of which pointed to an increase in
oxidative stress and inflammatory signaling. These changes resulted in an exacerbation of a dietary model of
NAFLD. This provides the first evidence that localized enteric viral infection can significantly alter the outcome
of a clinically relevant liver disease model. The goal of this proposal is to gain mechanistic insight into how this
occurs.
In this fellowship proposal, I aim to 1) determine the role of increased reactive oxygen species in MNV-
mediated metabolic changes, 2) identify the immune signaling pathways responsible for MNV effects on the
liver, and 3) determine which viral factors are required for the metabolic phenotype. Establishing the role of the
gut virome in mammalian biology is important to our understanding of the microbiome. Moreover, noroviral
infection is widespread in the human population and this research will highlight its relevance as a risk factor in
metabolic diseases.

## Key facts

- **NIH application ID:** 10063430
- **Project number:** 5F31HL149238-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Eugene Rudensky
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,019
- **Award type:** 5
- **Project period:** 2019-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063430

## Citation

> US National Institutes of Health, RePORTER application 10063430, Modulation of host metabolism by a persistent enteric virus (5F31HL149238-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10063430. Licensed CC0.

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