# Rotavirus interaction with gut intraepithelial lymphocytes

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2024 · $155,500

## Abstract

Project Summary
 Small bowel intestinal epithelial cells (IECs) are the first line of defense against human enteric viruses, the
most common and leading causes of diarrhea and death in infants and young children. How IECs
communicate with intraepithelial lymphocytes (IELs) in the small intestine and orchestrate antiviral responses
is heavily understudied. Our overall objectives are to better define the host immune signaling pathways in the
gastrointestinal tract during infections and to use that information to develop therapeutic interventions to
alleviate diarrhea and sequelae.
 Our preliminary results contrasted our expectation and demonstrated that the numbers of two IEL subsets
are significantly reduced during early rotavirus infection in vivo. We also found that rotavirus infection alters the
expression of several pro-inflammatory chemokines in infected human and mouse IECs. Based on these data
and prior publications, we hypothesize that the IELs are important mediators of host defense against
rotavirus infection and that rotavirus-encoded factors antagonize the antiviral activity of IELs in the
host small intestine via inhibition of chemokine expression.
 Testing these hypotheses is currently hampered by the lack of suitable model systems. Accordingly, we
have developed a highly tractable murine rotavirus reverse genetics method, a pathologically relevant neonatal
mouse model, and several innovative primary human and murine small bowel organoid culturing systems,
which will provide an unprecedented resolution of understanding of IEC-IEL crosstalk in the context of enteric
viral infections.
 In Aim 1, we will define a functional antiviral role of IELs in rotavirus infection in vivo using immunological
approaches and gene knockout mice. In Aim 2, we will identify the potential mechanism by which viral factors
dampen chemokine expression in infected IECs. Collectively, we expect these studies to establish a new
paradigm of mucosal antiviral immunity, especially early in life when most enteric infections occur. We also
expect to identify novel rotavirus immune evasion strategies, which will inform new strategies to develop host-
based broad-spectrum antiviral therapeutics and next-generation vaccine candidates.

## Key facts

- **NIH application ID:** 10877934
- **Project number:** 5R21AI173601-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Siyuan Ding
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $155,500
- **Award type:** 5
- **Project period:** 2023-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10877934

## Citation

> US National Institutes of Health, RePORTER application 10877934, Rotavirus interaction with gut intraepithelial lymphocytes (5R21AI173601-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10877934. Licensed CC0.

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