# Innate immunity to enteric virus infection by IFN?-stimulated-gene expression

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $385,000

## Abstract

Project Summary - Innate immunity to enteric virus infection by IFNλ-stimulated-gene expression
Antiviral immunity in the intestine and other mucosal surfaces faces a distinct challenge: clearance of viral
infection while maintaining barrier function and tolerance of the bacterial microbiome. To maintain this balance,
immune mechanisms with specificity to mucosal surfaces have evolved. Interferon lambda (IFNλ) stimulates
antiviral responses in intestinal epithelial cells (IECs) and is a critical component of intestinal immunity in
mouse models of norovirus (MNV) and rotavirus (MRV) infection; this requirement for IFNλ in control of these
enteric virus infections distinguishes it from other interferon types. Additionally, the bacterial microbiome
promotes MNV infection in an IFNλ receptor- (IFNLR) dependent manner, suggesting that the microbiome
alters the IFNλ-stimulated antiviral response. This proposal aims to close the gap in our understanding
regarding transcriptional programs unique to IFNλ, the effect of the bacterial microbiome on those
transcriptional programs, and the specific interferon stimulated genes (ISGs) required for viral control. Specific
Aim 1 will comprehensively characterize the transcriptional response in IECs and identify the genes necessary
for cell-intrinsic control of rotavirus infection. Specific Aim 2 will use novel intestinal macrophage and IEC co-
culture system to identify mechanisms by which IFNλ stimulates cell-extrinsic clearance of MNV. Specific Aim
3 will determine the role of the commensal microbiome in regulation of IFNλ-stimulated antiviral responses.
The long-term goal of this work is to discover novel aspects of IFN biology and its regulation in the
intestine that will aid in rational development of antivirals and immunotherapies.

## Key facts

- **NIH application ID:** 9918845
- **Project number:** 5R01AI130055-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Timothy J. Nice
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2017-05-09 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918845

## Citation

> US National Institutes of Health, RePORTER application 9918845, Innate immunity to enteric virus infection by IFN?-stimulated-gene expression (5R01AI130055-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9918845. Licensed CC0.

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