# Characterization of a commensal enteric virus

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $562,142

## Abstract

PROJECT SUMMARY
Accumulating evidence support the role of bacterial members of the gut microbiota in host defense and a variety
of immune disorders, such as inflammatory bowel disease (IBD). The mammalian gastrointestinal tract also
harbors diverse animal viruses. Despite their ubiquitous presence, the functional and mechanistic consequences
of intestinal colonization by viruses beyond their role as diarrheal pathogens has been unclear. Over the previous
funding periods of this award, we developed the murine norovirus (MNV) model as a tractable experimental
system to address this major gap in our knowledge. We found that MNV can function as a symbiotic virus by
providing benefits to the host, such as protection against secondary bacterial infection. At the same time, MNV
induces intestinal abnormalities in mice with a mutation in Atg16L1, an IBD susceptibility gene that participates
in the cellular degradative pathway of autophagy. The main objective of this proposal is to use the MNV model
to define the mechanisms that determine whether intestinal colonization by a viral symbiont leads to beneficial
or adverse outcomes for the host. We introduce data showing that MNV infection can significantly improve
survival of newly weaned mice from lethal infection by the Gram-negative bacterial pathogen Citrobacter
rodentium. We propose to use this model to elucidate how RNA sensing pathways are induced by a viral
symbiont to mediate cross-protection during early-life infection by an enteric bacterial pathogen, a leading cause
of mortality. In parallel, we will investigate how Atg16L1 mutation makes an otherwise beneficial virus become
harmful. Our preliminary data suggests a novel mechanism in which MNV infection replaces anti-inflammatory
lymphocytes in the gut with cytotoxic subsets that induce necrotic death of Paneth cells, a key secretory epithelial
cell implicated in human IBD. Defining the mechanistic details of these processes will yield new insight into the
nature of a viral symbiont in the gut, and may reveal new pathways involved in the resolution of tissue injury that
are distinct from those previously examined during bacterial colonization.

## Key facts

- **NIH application ID:** 10133411
- **Project number:** 2R01DK093668-10
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Ken Hashigiwa Cadwell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $562,142
- **Award type:** 2
- **Project period:** 2011-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133411

## Citation

> US National Institutes of Health, RePORTER application 10133411, Characterization of a commensal enteric virus (2R01DK093668-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10133411. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*