TY  - JOUR
AU  - Fehlinger, Andrea
AU  - Wolf, Hanna
AU  - Hossinger, André
AU  - Dürnberger, Yvonne
AU  - Pleschka, Catharina
AU  - Riemschoß, Katrin
AU  - Liu, Shu
AU  - Bester, Romina
AU  - Paulsen, Lydia
AU  - Priola, Suzette A
AU  - Groschup, Martin H
AU  - Schätzl, Hermann M
AU  - Vorberg, Ina M
TI  - Prion strains depend on different endocytic routes for productive infection.
JO  - Scientific reports
VL  - 7
IS  - 1
SN  - 2045-2322
CY  - [London]
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - DZNE-2020-06129
SP  - 6923
PY  - 2017
AB  - 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.
KW  - Animals
KW  - Biological Transport
KW  - Caveolin 1: metabolism
KW  - Cell Line
KW  - Cell Membrane: metabolism
KW  - Endocytosis
KW  - Mice
KW  - PrPSc Proteins: metabolism
KW  - PrPSc Proteins: pathogenicity
KW  - Prion Diseases: metabolism
KW  - Cav1 protein, mouse (NLM Chemicals)
KW  - Caveolin 1 (NLM Chemicals)
KW  - PrPSc Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:28761068
C2  - pmc:PMC5537368
DO  - DOI:10.1038/s41598-017-07260-2
UR  - https://pub.dzne.de/record/139807
ER  -