Protein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells, thereby templating their own aberrant conformation onto soluble homotypic proteins. Proteopathic seeds can be released into the extracellular space, secreted in association with extracellular vesicles (EV) or exchanged by direct cell-to-cell contact. The extent to which each of these pathways contribute to the prion-like spreading of protein misfolding is unclear. Exchange of cellular cargo by both direct cell contact or via EV depends on receptor-ligand interactions. We hypothesized that enabling these interactions through viral ligands enhances intercellular proteopathic seed transmission. Using different cellular models propagating prions or pathogenic Tau aggregates, we demonstrate that vesicular stomatitis virus glycoprotein and SARS-CoV-2 spike S increase aggregate induction by cell contact or ligand-decorated EV. Thus, receptor-ligand interactions are important determinants of intercellular aggregate dissemination. Our data raise the possibility that viral infections contribute to proteopathic seed spreading by facilitating intercellular cargo transfer. Pathologic protein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells via extracellular vesicles or direct cell-to-cell contact. Here, Liu et al. show that viral glycoproteins can contribute to intercellular proteopathic seed transmission via both routes.
【저자키워드】 Mechanisms of disease, neurodegeneration, 【초록키워드】 viral infection, Transmission, Proteins, Protein, cells, pathway, glycoprotein, extracellular vesicle, dissemination, disease, interactions, vesicular stomatitis virus, SARS-CoV-2 spike, association, cellular, Interaction, Contact, determinant, transfer, exchange, pathogenic, aggregate, aggregates, Protein misfolding, Cell, extracellular space, ENhance, raise, contribute, released, neurodegenerative, intercellular, secreted, viral glycoprotein, viral ligand, 【제목키워드】 Interaction, Protein misfolding, intercellular,