title: Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery.
abstract: Extracellular vesicles (EVs) have emerged as crucial mediators of intercellular communication, being involved in a wide array of key biological processes. Eukaryotic cells, and also bacteria, actively release heterogeneous subtypes of EVs into the extracellular space, where their contents reflect their (sub)cellular origin and the physiologic state of the parent cell. Within the past 20 years, presumed subtypes of EVs have been given a rather confusing diversity of names, including exosomes, microvesicles, ectosomes, microparticles, virosomes, virus-like particles, and oncosomes, and these names are variously defined by biogenesis, physical characteristics, or function. The latter category, functions, in particular the transmission of biological signals between cells in vivo and how EVs control biological processes, has garnered much interest. EVs have pathophysiological properties in cancer, neurodegenerative disorders, infectious disease, and cardiovascular disease, highlighting possibilities not only for minimally invasive diagnostic applications but also for therapeutic interventions, like macromolecular drug delivery. Yet, in order to pursue therapies involving EVs and delivering their cargo, a better grasp of EV targeting is needed. Here, we review recent progress in understanding the molecular mechanisms underpinning EV uptake by receptor-ligand interactions with recipient cells, highlighting once again the overlap of EVs and viruses. Despite their highly heterogeneous nature, EVs require common viral entry pathways, and an unanticipated specificity for cargo delivery is being revealed. We discuss the challenges ahead in delineating specific roles for EV-associated ligands and cellular receptors.
authors.affiliation: Department of Pathology, Exosomes Research Group, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Helena M
authors.initials: HM
authors.lastname: van Dongen
authors.affiliation: Department of Pathology, Exosomes Research Group, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Niala
authors.initials: N
authors.lastname: Masoumi
authors.affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA kwitwer1@jhmi.edu d.pegtel@vumc.nl.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Witwer
authors.affiliation: Department of Pathology, Exosomes Research Group, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands kwitwer1@jhmi.edu d.pegtel@vumc.nl.
authors.forename: D Michiel
authors.initials: DM
authors.lastname: Pegtel
mesh_terms: D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D016503:Drug Delivery Systems; D004705:Endocytosis; D000067128:Extracellular Vesicles / Q000502:physiology*; D006801:Humans; D011991:Receptors, Virus / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D011991:Receptors, Virus