A change in the conformation of prions accompanies the emergence of a new prion strain.
To investigate the role of the pathogenic prion protein (PrP(Sc)) in controlling susceptibility to foreign prions, two Syrian hamster (SHa) prion strains, Sc237 and DY, were transmitted to transgenic mice expressing chimeric SHa/mouse PrP genes, Tg(MH2M). First passage of SHa(Sc237) prions exhibited prolonged incubation times, diagnostic of a species barrier. PrP(Sc) of the new MH2M(Sc237) strain possessed different structural properties from those of SHa(Sc237), as demonstrated by relative conformational stability measurements. This change was accompanied by a disease phenotype different from the SHa(Sc237) strain. Conversely, transmission of SHa(DY) prions to Tg(MH2M) mice showed no species barrier, and the MH2M(DY) strain retained the conformational and disease-specific properties of SHa(DY). These results suggest a causal relationship between species barriers, changes in PrP(Sc) conformation, and the emergence of new prion strains.
Peretz
David
D
Institute for Neurodegenerative Diseases, Department of Neurology, University of California, San Francisco, CA 94143, USA.
Williamson
R Anthony
RA
Legname
Giuseppe
G
Matsunaga
Yoichi
Y
Vergara
Julie
J
Burton
Dennis R
DR
DeArmond
Stephen J
SJ
Prusiner
Stanley B
SB
Scott
Michael R
MR
D000818:Animals; D001921:Brain / Q000473:pathology; D006224:Cricetinae; D003433:Crosses, Genetic; D006041:Goats; D006801:Humans; D008647:Mesocricetus; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D018620:PrPSc Proteins / Q000737:chemistry* / Q000235:genetics; D017096:Prion Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000635:transmission*; D011487:Protein Conformation; D051381:Rats; D013045:Species Specificity
D018620:PrPSc Proteins