Protein Cargo and Antiviral Properties of Epithelial-derived EVs in RSV Infection

Our laboratory has pioneered work focused on the isolation and structural characterization of subcellular fractions known as extracellular vesicles (EVs), which are released by airway epithelial cells (AECs) under different experimental conditions. The applicant has published initial evidence that: 1) EVs from viral-infected human AECs contain both type I and type III interferons (IFNs), which are biologically active and inhibit viral replication in recipient cells; and 2) EVs can be isolated from upper airway secretions of patients with episodes of respiratory viral infections. The immune cargo of upper airway EVs and its antiviral activity are largely uncharacterized and therefore are central to this proposal EVs have a stable and “protective” structure, i.e., proteins that are carried within EVs can travel to distant sites and maintain their biological function. As such, our studies of EVs produced by HNOs and testing their antiviral properties on target lung cells will establish a novel and uncharted model of communication between the upper airways and the lung, highly relevant not only in the context of viral respiratory infections, but also in other diseases of the respiratory tract, such as asthma and COPD, which are often triggered by initial infectious episodes occurring in the upper airways. Characterization of EVs isolated from NPS of viral-infected children will provide an important translational correlate of our studies in HNOs.