Scientific Reports (Jul 2017)

Prion strains depend on different endocytic routes for productive infection

  • Andrea Fehlinger,
  • Hanna Wolf,
  • André Hossinger,
  • Yvonne Duernberger,
  • Catharina Pleschka,
  • Katrin Riemschoss,
  • Shu Liu,
  • Romina Bester,
  • Lydia Paulsen,
  • Suzette A. Priola,
  • Martin H. Groschup,
  • Hermann M. Schätzl,
  • Ina M. Vorberg

DOI
https://doi.org/10.1038/s41598-017-07260-2
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 15

Abstract

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Abstract Prions are unconventional agents composed of misfolded prion protein that cause fatal neurodegenerative diseases in mammals. Prion strains induce specific neuropathological changes in selected brain areas. The mechanism of strain-specific cell tropism is unknown. We hypothesised that prion strains rely on different endocytic routes to invade and replicate within their target cells. Using prion permissive cells, we determined how impairment of endocytosis affects productive infection by prion strains 22L and RML. We demonstrate that early and late stages of prion infection are differentially sensitive to perturbation of clathrin- and caveolin-mediated endocytosis. Manipulation of canonical endocytic pathways only slightly influenced prion uptake. However, blocking the same routes had drastic strain-specific consequences on the establishment of infection. Our data argue that prion strains use different endocytic pathways for infection and suggest that cell type-dependent differences in prion uptake could contribute to host cell tropism.