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

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $453,516

## Abstract

ABSTRACT
Gastrointestinal diseases caused by enteric viral pathogens such as norovirus and rotavirus impose a
significant global health burden and can be lethal in vulnerable populations. For these and other viral
pathogens, interferon (IFN) family cytokines are among the most potent elements of the antiviral immune
response. Thus, IFN pathways are clinically relevant targets for treatment of disease, and are an important
area for continued foundational research. We and others have shown that the most recently discovered type of
IFN (type III IFN, IFN-λ) promotes innate antiviral immunity in intestinal epithelial cells (IECs) while minimizing
inflammatory damage that can accompany a type I IFN response. Our most recent work has now identified a
homeostatic IFN-λ response, stimulated by bacterial microbiota, that elicits antiviral genes within pockets of
intestinal epithelium prior to viral exposure. Our studies of mouse rotavirus infection suggest that homeostatic
IFN-λ preemptively limits viral infection of IECs. The objective of this research proposal is to define the cellular
source of homeostatic IFN-λ production in the intestine (aim 1), the mechanistic basis for its expression (aim
2), and its impact on enteric viral disease (aim 3). Based on our prior work and preliminary studies, our central
hypothesis is that intestinal dendritic cells produce homeostatic IFN-λ during transient exposure to bacterial
products, promoting preemptive antiviral responses in epithelial cells. Through the studies of this research
project, we will identify the basis of the localized homeostatic IFN-λ response in IECs, thereby advancing our
fundamental understanding of this IFN type in the antiviral immunity to enteric viral pathogens.

## Key facts

- **NIH application ID:** 10583367
- **Project number:** 2R01AI130055-06A1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Timothy J. Nice
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $453,516
- **Award type:** 2
- **Project period:** 2017-05-09 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10583367

## Citation

> US National Institutes of Health, RePORTER application 10583367, Innate immunity to enteric virus infection by IFN-lambda stimulated-gene expression (2R01AI130055-06A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10583367. Licensed CC0.

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