The endoplasmic reticulum as a cradle for virus and extracellular vesicle secretion

Extracellular vesicles (EVs) are small membranous carriers of protein, lipid, and nucleic acid cargoes and play a key role in intercellular communication. Recent work has revealed the previously under-recognized participation of endoplasmic reticulum (ER)-associated proteins (ERAPs) during EV secretion, using pathways reminiscent of viral replication and secretion. Here, we present highlights of the literature involving ER/ERAPs in EV biogenesis and propose mechanistic parallels with ERAPs exploited during viral infections. We propose that ERAPs play an active role in the release of EVs and viral particles, and we present views on whether viruses hijack or enhance pre-existing ERAP-dependent secretory machineries or whether they repurpose ERAPs to create new secretory pathways.