Autophagy promotes release of progeny rhinovirus in microvesicles and not viral replication in airway epithelial cell cultures 2196

Abstract Description COPD airway epithelial cell cultures show higher viral load following RV infection in both extracellular and intracellular compartment despite expressing antiviral IFNs and IFN-stimulated genes. Autophagy plays a role in viral replication and releasing progeny virus. Since COPD airway epithelial cells show increased autophagy under basal conditions, we examined the role of autophagy in enhancing the viral load in these cells. RV-infected COPD mucociliary-differentiated airway epithelial cell cultures released microvesicles enriched in infectious progeny compared to normal cultures. Following RV infection normal, but not COPD cell culture showed increase in autophagy. Inhibition of autophagy by pharmacological inhibitor 3MA reduced microvesicles containing progeny virions in both COPD and normal cultures, but did not affect total viral load. Further, genetic inhibition of LC3β, a component of autophagy vesicles cells showed a reduction in microvesicles containing virus and not total viral load. Genetic inhibition of viral receptor ICAM-1 did not affect the cellular entry of microvesicle bound virus. These results indicate the contribution of autophagy in the release of microvesicles containing progeny virions without causing cell death and that persistent autophagy in COPD may promote the release of microvesicles enriched in progeny virions. Since virions in microvesicles are not readily degraded, they can infect the neighboring cells efficiently and spread viral infection. Funding Sources NIH AT009991 Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)