Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions
| Autor: | Shu Liu, Annika Hornberger, Katerina Konstantoulea, Philip Denner, Stefan F. Lichtenthaler, Stefanie-Elisabeth Heumüller, Lydia Paulsen, André Hossinger, Joost Schymkowitz, Frederic Rousseau, Ina Vorberg, Manuela Neumann, Oleksandra Buravlova, Stephan A. Müller |
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| Rok vydání: | 2020 |
| Předmět: |
metabolism [Viral Envelope Proteins]
Male Protein Folding ALPHA-SYNUCLEIN Intravital Microscopy PRION General Physics and Astronomy Protein aggregation metabolism [Angiotensin-Converting Enzyme 2] metabolism [Extracellular Vesicles] Viral Envelope Proteins pathology [Brain] chemistry.chemical_classification Multidisciplinary Membrane Glycoproteins biology UNCONVENTIONAL SECRETION Chemistry food and beverages Brain spike protein SARS-CoV-2 IMMUNODEFICIENCY-VIRUS TYPE-1 Middle Aged Endocytosis Cell biology ddc Multidisciplinary Sciences ALZHEIMERS-DISEASE Article Mechanisms of disease Neurodegeneration Vesicular stomatitis virus Spike Glycoprotein Coronavirus Science & Technology - Other Topics Protein folding Female ddc:500 Angiotensin-Converting Enzyme 2 Intracellular Adult Prions Science ACE2 protein human tau Proteins MEMBRANE-FUSION Protein Aggregation Pathological General Biochemistry Genetics and Molecular Biology virology [Protein Aggregation Pathological] Cell Line Extracellular Vesicles pathology [Protein Aggregation Pathological] Extracellular Humans Aged G protein vesicular stomatitis virus EXOSOMES Science & Technology EXTRACELLULAR VESICLES General Chemistry biology.organism_classification metabolism [tau Proteins] Cell culture metabolism [Spike Glycoprotein Coronavirus] Case-Control Studies metabolism [Prions] CELLS TAU Glycoprotein metabolism [Membrane Glycoproteins] |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) Nature Communications 12(1), 5739 (2021). doi:10.1038/s41467-021-25855-2 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-021-25855-2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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