# Molecular Mechanisms and In Vivo Impact of Tethered Mucin 1-Influenza Virus Interactions

> **NIH NIH R01** · UNIV OF MARYLAND, COLLEGE PARK · 2022 · $617,953

## Abstract

ABSTRACT
To infect airway epithelial cells, influenza A virus (IAV) must penetrate the secreted mucus and underlying
periciliary layer barriers – both comprised, in large part, of mucin glycoproteins that can be secreted or tethered
to the apical surface of cells. The importance of tethered mucins in various disease states and acute infection
is increasingly being realized. Specifically, tethered mucin 1 (MUC1) has been implicated in various aspects of
both bacterial and viral infections. However, these reports do not yield consensus on MUC1 function during
pathogenic insult and while it seems logical to assume that MUC1 expression would benefit the host, our
preliminary data indicate that MUC1 facilitates IAV infection. As MUC1 is expressed by multiple cell types that
influence IAV pathogenesis, including airway epithelial cells and macrophages, and has been proposed to act
as both a structural barrier and signaling molecule, we hypothesize that MUC1 facilitates IAV infection through
multiple mechanisms, involving both physical and functional attributes of MUC1, and multiple cell types. We
will test this hypothesis by pursing two specific aims: 1) Define the contribution of MUC1 expression in specific
cell compartments to IAV pathogenesis and 2) Define MUC1 molecular interactions and intracellular dynamics
in human airway epithelium during IAV infection. Aim 1 will generate a MUC1-expression atlas in the lung
during infection, determine the impact of MUC1 expression on IAV infection of both human and mouse primary
airway epithelial cells, and define the contribution of MUC1 expression in specific cell compartments to the
outcome of infection in vivo. Aim 2 will interrogate the physical interaction between IAV and MUC1 in
physiologically relevant models of airway epithelium and define the impact of IAV and interferon on MUC1
expression, activation, and interacting partners through mechanistic studies and comprehensive mass
spectrometry-based technology. This research is innovative in its use of novel in vitro and in vivo models with
altered MUC1 expression to dissect the interplay between IAV and MUC1 at both the molecular and
organismal level. Our results will be significant as defining MUC1 function in the context of IAV infection will
advance our understanding of tethered mucin biology and reveal mechanisms of how IAV negotiates specific
mucin molecules to efficiently infect the respiratory tract.

## Key facts

- **NIH application ID:** 10327722
- **Project number:** 5R01HL151840-02
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Margaret Adele Scull
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $617,953
- **Award type:** 5
- **Project period:** 2021-01-15 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327722

## Citation

> US National Institutes of Health, RePORTER application 10327722, Molecular Mechanisms and In Vivo Impact of Tethered Mucin 1-Influenza Virus Interactions (5R01HL151840-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10327722. Licensed CC0.

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