Cell-free formation of misfolded prion protein with authentic prion infectivity.
Prion propagation has been modeled in vitro; however, the low infectious titer of PrP(Sc) thus generated has cast doubt on the "protein-only" hypothesis. Here we show that prion delivery on suitable nitrocellulose carrier particles abrogates the apparent dissociation of PrP(Sc) and infectivity. Misfolded prion protein generated by protein misfolding cyclic amplification is as infectious as authentic brain-derived PrP(Sc) provided that confounding effects related to differences in the size distribution of prion protein aggregates generated in vitro and consecutive differences in regard to biological clearance are abolished.
Weber
Petra
P
Center for Neuropathology and Prion Research, Ludwig Maximilians University of Munich, Feodor-Lynen-Strasse 23, 81377 Munich, Germany.
Giese
Armin
A
Piening
Niklas
N
Mitteregger
Gerda
G
Thomzig
Achim
A
Beekes
Michael
M
Kretzschmar
Hans A
HA
D000818:Animals; D001681:Biological Assay; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002474:Cell-Free System; D003101:Collodion; D006224:Cricetinae; D051379:Mice; D008810:Mice, Inbred C57BL; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000378:metabolism* / Q000472:pathogenicity*; D017510:Protein Folding; D015996:Survival Rate
D011328:Prions; D003101:Collodion