# Effects of wildfire smoke on respiratory antiviral defense responses

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $607,668

## Abstract

PROJECT SUMMARY
Wildfire smoke increasingly contributes to ambient air pollution and more specifically PM2.5 and has been
associated with increased respiratory virus morbidity and mortality. We have previously shown that exposure of
human volunteers to woodsmoke (WS) significantly modifies acute antiviral host defense responses to influenza.
Similarly, we have preliminary evidence indicating that simulation of wildfire smoke affects viral infections in
human nasal epithelial cells (HNECs) in vitro. Since concurrent exposures to wildfires and respiratory viruses
will likely increase worldwide due to climate change, understanding the clinical manifestation, cellular
mechanisms, and chemical components causing modified antiviral defense presents an important research gap
critical to public health. We have already demonstrated that computational modeling approaches can establish
the presence of harmful chemicals in different wildfire smoke conditions as drivers of toxicity. Integrating these
translational research and computational analysis models, the central hypothesis of this proposal is that wildfire
smoke affects multiple steps of antiviral defense pathways in the respiratory mucosa and that chemical
signatures within the complex pollutant mixtures can be associated as drivers of biological responses. Specific
Aim 1 will use in vitro exposure and infection of HNECs to determine the mechanisms of wildfire smoke-induced
changes in antiviral defense function and identify the chemical signatures mediating these responses. HNECs
will be exposed to a variety of different emission mixtures simulating different wildfire scenarios. Changes in viral
infection and multi-omic assessment of immune and inflammatory responses will be assessed. Using
computational modeling, chemical and molecular signatures driving the responses in HNECs in vitro will be
determined. Specific Aim 2 will determine the effects of WS exposures and influenza infection on nasal immunity
in humans in vivo, using inoculation with the live attenuated influenza virus (LAIV) vaccine as a model to elicit
antiviral defense responses in the respiratory mucosa. Volunteers will be randomized for exposures to
WS/Filtered Air followed by inoculation with LAIV/Placebo. Using multi-omic platforms, samples will be analyzed
for immune biomarkers, as well as markers of viral replication and sinonasal symptoms, followed by
computational analysis associating biomarkers with infection outcomes. This application aims to
comprehensively assess the impact of wildfires on respiratory mucosal antiviral defenses by examining viral
entry and replication, antibody production, as well as mucosal metabolomics, transcriptomics, and proteomics
mediating cellular defenses. The parallel investigations of in vitro (SA1) and clinical (SA2) outcomes will yield
both immediate translational impact and in-depth mechanistic insights into the effects of wildfires on respiratory
antiviral defenses. Ultimately, this applicatio...

## Key facts

- **NIH application ID:** 10857691
- **Project number:** 1R01ES036209-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Meghan Elizabeth Rebuli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $607,668
- **Award type:** 1
- **Project period:** 2024-08-10 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10857691

## Citation

> US National Institutes of Health, RePORTER application 10857691, Effects of wildfire smoke on respiratory antiviral defense responses (1R01ES036209-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10857691. Licensed CC0.

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