Golgi-derived extracellular vesicle production induced by SARS-CoV-2 envelope protein.

Extracellular vesicles 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 vesicles (2-E-EVs). Although 2-E-EVs have been demonstrated to facilitate viral transmission in a receptor-independent way, the characteristics and biogenesis mechanism remain enigmatic. Via lipidomics and proteomic analysis, we found 2-E-EVs are distinct from endosome-derived exosomes. 2-E-EVs are 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-EVs formation, Golgi fragmentation, and channel activity, emphasizing the role of 2-E-EVs as ion channel-induced extracellular vesicles. 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.