# Surfactant Protein and Lipid Inhibition of Respiratory Virus Infections

> **NIH NIH U19** · UNIVERSITY OF ARIZONA · 2020 · $317,000

## Abstract

Abstract
Virus-induced exacerbations of asthma are a major cause of emergency room visits and hospitalizations, and
contribute disproportionately to the economic burden of the disease. Rhinovirus (RV) is a dominant instigator
of exacerbations, and other respiratory viruses, including Respiratory Syncytial Virus (RSV), for which no
vaccine is available, also contribute significantly to the incidence of exacerbations. In this Project we will
focus upon inhibitors of RV and RSV infection of nasal and bronchial epithelial cells cultured from adult control
and asthmatic subjects. Two endogenous molecules of the pulmonary surfactant system, surfactant protein A
(SP-A) and palmitoyl-oleoyl-phosphatidylglycerol (POPG), act as potent antagonists of RV and RSV infection.
In this proposal we will examine the protective activity of these surfactant constituents in preventing viral
infections of differentiated nasal and bronchial epithelial cells, derived from control and asthmatic subjects.
Preliminary data demonstrate that SP-A binds to RV with high affinity and inhibits infection of epithelial cells.
We will elucidate the mechanism of SP-A inhibition of RV infection. The SP-A binding to RV is isoform
dependent and we will investigate whether the genetic makeup of the asthmatics in our cohorts is skewed
towards SP-A variants that exhibit weak binding to RV. POPG inhibits RV and also RSV infection of epithelial
cells, and we will determine the mechanism of anti-viral action of this lipid. The proposed experiments will
also reveal if epithelial cells from asthmatic are either sensitive or inherently resistant to the protective actions
of the surfactant constituents. Our studies with SP-A and POPG will be integrated with other projects in the
overall proposal. All of the subject derived epithelial cells will be provided by the Clinical Core. In
collaborative studies with Project 1, we will determine the action of SP-A isoforms as inhibitors of IL-13
signaling. We will also investigate the effectiveness of SP-A isoforms and POPG as antagonists of RV
infections and inflammatory sequelae in the presence of high levels of IL-13 that mimic the asthmatic
environment in vivo. In collaborative studies with Project 2 we will determine if SP-A and POPG can suppress
the elevated inflammatory phenotype of Tollip deficient epithelial cells. The final goal of this project is to
critically test the in vivo activity of SP-A and POPG using a mouse model of asthma exacerbation that
combines priming with house dust mite allergen followed by challenge with RV, or RSV. The in vivo
experiments will provide important new information about the potential application of SP-A and POPG for the
prevention and treatment of virus -elicited exacerbations of asthma in humans.

## Key facts

- **NIH application ID:** 9971439
- **Project number:** 5U19AI125357-05
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** DENNIS R. VOELKER
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $317,000
- **Award type:** 5
- **Project period:** — → 2021-08-23

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971439

## Citation

> US National Institutes of Health, RePORTER application 9971439, Surfactant Protein and Lipid Inhibition of Respiratory Virus Infections (5U19AI125357-05). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/9971439. Licensed CC0.

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