# Viral immune evasion during intestinal norovirus infection

> **NIH NIH R01** · BROWN UNIVERSITY · 2024 · $567,727

## Abstract

Project Summary/Abstract
 Sensing viral infections in epithelial cells plays a crucial role in the frontline defense against enteric viral
infections. The RIG-I like receptors (RLRs) act as critical sensors for RNA viral infections by inducing interferon
signaling. While there has been extensive research on the cell intrinsic regulation of the RLR sensing pathway
and viral evasion, the role of neighboring bystander cells in robust interferon (IFN) responses from the RLR
sensing pathway remains understudied.
 This research proposal aims to utilize a murine norovirus (MNoV) infection model in mice to demonstrate
a key immune evasion strategy for the global suppression of the RLR sensing pathway. Preliminary results from
this study propose a novel concept of intestinal epithelial sensing of viral infection and evasion of viral RNA
sensing, highlighting the importance of non-tuft bystander enterocytes for IFN-λ responses as well as the viral
counteraction through the utilization of a cellular receptor for the secreted viral protein NS1 to suppress the RIG-
I/MDA5 pathway.
 We identified Syndecan-4 as a putative cellular receptor for the virokine NS1. The central hypothesis of
this research proposal is that the secreted virokine NS1 achieves tissue-wide suppression of the antiviral RIG-
I/MDA5 sensing pathway through direct binding to the cellular receptor SDC4 on the epithelial cell surface. The
proposal aims to explore how NS1 mediates the suppression of RIG-I/MDA5-IFN-λ immunity and the
physiological relevance of this host-virus interaction.

## Key facts

- **NIH application ID:** 10858313
- **Project number:** 1R01AI183155-01
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Sanghyun Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $567,727
- **Award type:** 1
- **Project period:** 2024-03-06 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10858313

## Citation

> US National Institutes of Health, RePORTER application 10858313, Viral immune evasion during intestinal norovirus infection (1R01AI183155-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10858313. Licensed CC0.

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