# Pulmonary Surfactant Antagonists of Rhinovirus Infection and Inflammation

> **NIH NIH P01** · NATIONAL JEWISH HEALTH · 2020 · $387,691

## Abstract

Viral exacerbations of asthma are responsible for 1.8 million emergency room visits and 0.4 million 
hospitalizations in the US each year, constituting a major public health problem and economic burden. 
Human rhinoviruses (HRV) are the dominant instigators of asthma exacerbations in children and adults. 
Currently, there are not preventives or therapeutics for HRV infection. Our recent work has identified three 
constituents of human pulmonary surfactant, the phospholipids, palmitoyl-oleoyl-phosphatidylglycerol (POPG) 
and phosphatidylinositol (PI), and surfactant protein A (SP-A), as potent inhibitors of HRV infection and 
inflammatory sequelae. This proposal is focused upon defining how POPG, PI and SP-A inhibit viral infection 
in primary cultures of human nasal epithelial cells; and testing the efficacy of these agents for preventing 
exacerbations in mouse models of asthma. We will address these issues in three Specific Aims. In Aim 1 
we will investigate the molecular mechanisms of human SP-A inhibition of 3 types of HRV infection with special 
emphasis upon the isoforms of the protein that are most effective against each virus. We will examine the 
anti-viral activities of the three major expressed isoforms of human SP-A encoded by the SP-A1 gene, and the 
three major expressed isoforms encoded by the SP-A2 gene. In Aim 2 we will investigate the mechanisms of 
POPG and PI inhibition of three types of HRV infection and inflammation. In Aim 3 we will critically test the 
activities of PI and novel structural anaolgs of the lipid as inhibitors of HRV infection in mice. PI and structural 
analogs will also be examined for their activity as suppressors of asthma exacerbations, using a house dust 
mite model for asthma coupled with HRV infection in mice. The studies in this project will be integrated with 3 
other Research Projects, a Clinical Core and a Biostatistics/Environmental Exposure Core that are essential 
elements of the entire Research Proposal. The Clinical Core will provide patient nasal epithelial cells from 
exacerbation-prone asthmatics and multiple control groups. Project 1 will provide detailed information 
regarding the environmental exposures that drive asthma exacerbations and influence the phenotypes of the 
epithelial cells, and ultimately the clinical outcome of patients. We will interface with Project 2 by determining 
how SP-A, POPG, PI and lipid analog antagonism of HRV infection influences the transcriptomic profiles of the 
epithelial cells and if there are any associations with environmental exposures and clinical outcomes. Our 
interactions with Project 3 will focus upon how the interactions between SP-A and lipids influence the 
production and secretion of factors from nasal epithelial cells that influence the epigenetic landscape and 
phenotypes of CD4+ T cells. In total, Project 4 will provide new information about the anti-viral properties of 
pulmonary surfactant constituents and their utility for preventing ...

## Key facts

- **NIH application ID:** 10009465
- **Project number:** 5P01HL132821-04
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** Mari Numata-Nakamura
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,691
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10009465

## Citation

> US National Institutes of Health, RePORTER application 10009465, Pulmonary Surfactant Antagonists of Rhinovirus Infection and Inflammation (5P01HL132821-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10009465. Licensed CC0.

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