1. Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions
- Author
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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, and Stephan A. Müller
- Subjects
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] - Abstract
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.
- Published
- 2020