Golgi-derived extracellular vesicle production induced by Viral 2-E channels

Extracellular vesicles (EVs) facilitate cell-to-cell communication, and some enveloped viruses utilize these vesicles as carriers to mediate viral transmission. SARS-CoV-2 envelope protein (2-E) forms a cation channel and overexpression of 2-E led to the generation of a distinct type of large extracellular vesicle (2-E-EV). Although 2-E-EV has been demonstrated to facilitate viral transmission in a receptor-independent way, the characteristics and biogenesis mechanism remained enigmatic. We identified 2-E-EV as a novel EV. Via lipidomics and proteomic analysis, we found 2-E-EV is distinct from endosome-derived exosomes. 2-E-EV is notably enriched in Golgi apparatus components, aligning with the observed fragmentation in Golgi morphology. Through live cell imaging, we established a connection between 2-E-EV formation, Golgi fragmentation, and channel activity, emphasizing the role of 2-E-EV as an ion channel-induced extracellular vesicle. Our work highlights 2-E-EVs as distinctive Golgi-derived vesicles, contributing to a deeper understanding of 2-E channel-mediated virus-host dynamics, with implications for therapeutic strategies and drug delivery.