Glycoproteins on the surface of viruses, which aid their entry into target cells, may facilitate the spread of protein aggregates associated with neurodegenerative diseases, suggests a proof-of-concept study in mammalian cells published in Nature Communications. The findings, based on investigations involving two viruses, shed further light on the potential for cellular transmission of neurodegenerative diseases.
Misfolding and the accumulation of different proteins such as Tau are hallmarks of neurodegenerative diseases, including prion diseases, Alzheimer’s disease or Parkinson’s disease. Previous research has shown that proteopathic seeds (pathogenic protein aggregates) associated with neurodegenerative diseases have the ability to be transmitted to unaffected cells either by secretion of membrane-free naked aggregates as cargos of extracellular vesicles (EVs), or via direct cell-to-cell contact. The extent to which these individual processes aid transmission of proteopathic seeds to healthy cells is unknown.
Ina Vorberg and colleagues hypothesised that seed transmission involving membrane contacts as observed for EV transmission or in direct cell-to-cell contacts could be partially controlled at cell entry. Cell entry is mediated by the interaction between specific ligands (a molecule that binds to a protein receptor) and a cellular receptor on the surface of the target cell. This process is also observed when viral glycoproteins (that serve as ligands) bind to their cellular entry receptors to mediate viral entry. As a proof-of-concept the authors conducted experiments in mammalian cells using vesicular stomatitis virus (VSV) glycoprotein and the spike protein of SARS-CoV-2. They found that both viral glycoproteins enhanced the transmission of proteopathic seeds via EVs and cell-to-cell transmission. The authors suggest these findings highlight the potential of proteopathic seed transmission via mechanisms involving direct membrane contacts when equipped with suitable ligands, and may also indicate that viral infection may facilitate the spread of proteopathic seeds.
The authors conclude that further research is needed to investigate the effect of viruses on protein aggregation in neurodegenerative diseases.
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