# Extracellular Vesicles (EVs) Innate Immune Cargo in Respiratory Viral Infections

> **NIH NIH R21** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2024 · $240,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Developmental delay in the maturation of the innate immune system and in particular reduced functionality of
interferon (IFN) pathways are recognized mechanisms of disease severity following viral respiratory infections
in early life. Respiratory syncytial virus (RSV) in particular, represents the leading cause of severe lower
respiratory tract illness (LRTI) in young infants and children, with no therapies or vaccines currently available.
As part of our investigations focused on the isolation and structural characterization of epithelial-derived
subcellular fractions called extracellular vesicles (EVs) we discovered that EVs released from viral-infected
human airway epithelial cells contain biologically active type I and III IFNs, while EVs isolated from the upper
airways of patients with respiratory viral infections contain only type III IFN. EVs, a type of secretory vehicle
released from cells, are characterized by size and specific markers which has allowed their identification in
various human bio-fluids. EVs contain nucleic acids, lipids, and proteins, and have been shown to transfer this
biologically active cargo between neighboring cells and to distant sites, therefore participating in processes of
cell-to-cell communication, inflammation, and disease pathogenesis. Overall, little is known regarding the
characteristics of EVs generated in vivo in human airways, how viral respiratory infections such as those
caused by RSV shape the EVs structural and cargo-related characteristics, and whether they contribute to the
antiviral immune response. Based on our work and this gap in the knowledge, Specific Aim 1 will characterize
the innate immune cargo of EVs isolated from the nasopharyngeal secretions (NPS) of children with acute
RSV infections and from cultures of human nose organoids (HNOs)-derived epithelial cells. The biological
activity of NPS and HNO EVs and EV-expressed IFNs will be tested by state-of-the art antiviral assays in RSV-
infected recipient lung epithelial cells. Mechanistic studies in Specific Aim 2 will determine the contribution of
RSV F and G proteins carried by EVs and EV cargo of nucleic acids and their respective cytosolic receptor(s),
in the process of EV internalization, antiviral gene expression and overall induction of an antiviral status in
target/recipient cells. Our published work and preliminary data support the concept that the packaging of innate
immune mediators in EVs secreted in the upper airway mucosa represents an important and currently
unknown antiviral mechanism directed not only to adjacent areas but also to sites far from of initial viral entry or
infection, such as the lower respiratory tract and lung. The results of studies proposed in this exploratory R21
will inform a future R01, which will include studies in a large cohort of viral-infected infants to determine
correlation between EV-associated IFNs/innate mediators and viral load in the nasal mucosa, disease severity
an...

## Key facts

- **NIH application ID:** 10809195
- **Project number:** 1R21AI176085-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Roberto P Garofalo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $240,000
- **Award type:** 1
- **Project period:** 2024-06-18 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809195

## Citation

> US National Institutes of Health, RePORTER application 10809195, Extracellular Vesicles (EVs) Innate Immune Cargo in Respiratory Viral Infections (1R21AI176085-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10809195. Licensed CC0.

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