# Astrovirus modulation of gut immunity via goblet cells

> **NIH NIH K22** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2022 · $107,360

## Abstract

PROJECT SUMMARY
Astroviruses, positive-sense single-stranded RNA enteric viruses, are a leading cause of diarrhea worldwide.
In comparison to other viruses that cause diarrhea astroviruses do not cause overt pathology, cell death,
inflammation, or immune cell infiltration. We now believe this is related to their unique ability to infect small
intestinal goblet cells, specialized epithelial cells that produce the mucus barrier and play a central role in the
innate defenses of the gastrointestinal tract. Mucus not only protects against potential pathogens but also
modulates interactions of the epithelial layer with commensal bacteria to promote a symbiotic environment that
prevents self-digestion. Goblet cell dysfunction can trigger inflammation, and loss of the mucus barrier can
impair host defenses against gastrointestinal diseases. Although the molecular interactions between goblet
cells and bacteria have been characterized, few studies have focused on enteric virus interactions and their
role in gut health. To fill this gap in knowledge, I propose using the murine model for astrovirus to study their
unique tropism and the consequences of infection for gut health. My central hypothesis is that astrovirus
hijacks the secretory pathway of goblet cells and this alters goblet cell immune and homeostatic functions. To
test this hypothesis, in Aim 1 I will identify the molecular mechanisms by which astroviruses use secretory
goblet cells for replication and in Aim 2 I will determine how infection alters the ability of goblet cells to form the
mucus barrier and facilitate mucosal immune responses via the delivery of luminal antigens to the lamina
propria. These data will reveal an entirely new facet of host-pathogen interactions that will be critical to our
understanding of gut immunity and homeostasis in the context of viral infection.

## Key facts

- **NIH application ID:** 10456017
- **Project number:** 5K22AI156116-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Valerie Cortez
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $107,360
- **Award type:** 5
- **Project period:** 2021-07-23 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456017

## Citation

> US National Institutes of Health, RePORTER application 10456017, Astrovirus modulation of gut immunity via goblet cells (5K22AI156116-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10456017. Licensed CC0.

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