Presenter of 1 Presentation
EFFICIENT INTERCELLULAR DISSEMINATION OF PROTEOPATHIC SEEDS MEDIATED BY VIRAL GLYCOPROTEINS
Abstract
Aims
Cell-to-cell propagation of protein misfolding likely underlies the stereotypical pattern of disease progression in neurodegenerative disorders. Mechanisms of intercellular protein aggregate spreading are ill-defined, but include secretion of free protein aggregates, direct cell contact or release of pathologic protein aggregates in association with extracellular vesicles (EV). To which extent these pathways contribute to proteopathic seed spreading is so far unknown. Interestingly, EV can increase the dissemination of enveloped viruses by shuttling partial or whole genomes and even viral particles to uninfected cells. Here we tested the hypothesis if decoration of EV with viral glycoproteins could also contribute to the spreading of protein aggregates between cells.
Methods
Permanent and primary cells propagating self-templating protein aggregates and expressing viral glycoproteins served as donor cells to test their capacity to spread protein misfolding to cocultured recipient cells. Futher, recipient cells were exposed to viral glycoprotein-decorated donor EV.
Results
We here demonstrate that coating donor cells or EV with viral ligands from vesicular stomatitis virus or Cov-2 strongly increases aggregate induction in recipients. Increased aggregate induction was observed for both tau and prion models, arguing that viral glycoproteins affect intercellular spreading of diverse types of protein aggregates.
Conclusions
In light of findings that some viruses are upregulated in brains of patients suffering from neurodegenerative diseases, viral infections could potentially contribute to the dissemination of proteopathic seeds and ultimately modulate disease progression.