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10.1038/s41467-021-25855-2

http://scihub22266oqcxt.onion/10.1038/s41467-021-25855-2
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suck abstract from ncbi


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pmid34667166      Nat+Commun 2021 ; 12 (1): 5739
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  • Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions #MMPMID34667166
  • Liu S; Hossinger A; Heumuller SE; Hornberger A; Buravlova O; Konstantoulea K; Muller SA; Paulsen L; Rousseau F; Schymkowitz J; Lichtenthaler SF; Neumann M; Denner P; Vorberg IM
  • Nat Commun 2021[Oct]; 12 (1): 5739 PMID34667166show ga
  • 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.
  • |Adult[MESH]
  • |Aged[MESH]
  • |Angiotensin-Converting Enzyme 2/*metabolism[MESH]
  • |Brain/pathology[MESH]
  • |Case-Control Studies[MESH]
  • |Cell Line[MESH]
  • |Endocytosis[MESH]
  • |Extracellular Vesicles/*metabolism[MESH]
  • |Female[MESH]
  • |Humans[MESH]
  • |Intravital Microscopy[MESH]
  • |Male[MESH]
  • |Membrane Glycoproteins/*metabolism[MESH]
  • |Middle Aged[MESH]
  • |Prions/metabolism[MESH]
  • |Protein Aggregation, Pathological/pathology/*virology[MESH]
  • |Protein Folding[MESH]
  • |Spike Glycoprotein, Coronavirus/*metabolism[MESH]
  • |Viral Envelope Proteins/*metabolism[MESH]


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