Alterations in Lung Carcinoma Cells and Cell-Derived Extracellular Vesicles after Human Adenovirus Type 5 Administration

Abstract

Human adenoviruses (HAdVs) affect the respiratory system of healthy individuals and people with pre-existing health conditions. These highly infectious viruses can alter a myriad of cellular and pathophysiological processes. HAdVs can modulate their infection ability and pathogenicity by regulating extracellular vesicles (EVs) formation and function. EVs are nanovesicles that facilitate intracellular communication, cell signaling/trafficking, and immune regulation. We propose that HAdVs can exploit EV formation, secretion, and release various pathways to promote infection and transmission between neighboring cells. In the present study, we explored the impact of HAdV serotype 5 (HAdV-5) on the A549-epithelial carcinoma cells and EVs derived from A549 cells. A549 cells were cultured in an exosome-depleted medium and administered different concentrations of HAdV-5 at varying time points. The effect of HAdV-5 infection on A549 cells and A549-derived EVs was determined by 4’,6-diamidino2-phenylindole (DAPI) stain, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay, electron microscopy, particle size, zeta potential analysis, immunosorbent analysis, total RNA levels, and total protein content. Our findings illustrated that HAdV-5 reduces A549-cell viability and promotes variations within the protein content of A549 cells. Our data explicitly demonstrated that HAdV-5 significantly altered EV numbers, biogenesis, and composition. These findings suggest that HAdV-5 modulates EVs’ biological properties and physiological functions in human lung carcinoma cells.