ID 111465
Title Alternative
The Role of the OR Region in BSE Pathogenesis
Author
Miyata, Hironori University of Occupational and Environmental Health
Das, Nandita Rani Tokushima University
Yoshimochi, Tatenobu Tokushima University
Watanabe, Hitomi Kyoto University
Kondoh, Gen Kyoto University
Yokoyama, Takashi National Agriculture and Food Research Organization (NARO)
Keywords
Prion
Prion protein
Octapeptide repeat
Bovine spongiform encephalopathy (BSE)
Scrapie
Content Type
Journal Article
Description
Conformational conversion of the cellular isoform of prion protein PrPC, into the abnormally folded, amyloidogenic isoform, PrPSc, is a key pathogenic event in prion diseases including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals. We previously reported that the octapeptide repeat (OR) region could be dispensable for converting PrPC into PrPSc after infection with RML prions. We demonstrated that mice transgenically expressing mouse PrP with deletion of the OR region on the PrP-knockout background, designated Tg(PrPΔOR)/Prnp0/0 mice, did not reduced susceptibility to RML scrapie prions, with abundant accumulation of PrPScΔOR in their brains. We show here that Tg(PrPΔOR)/Prnp0/0 mice were highly resistant to BSE prions, developing the disease with markedly elongated incubation times after infection with BSE prions. The conversion of PrPΔOR into PrPScΔOR was markedly delayed in their brains. These results suggest that the OR region may have a crucial role in the conversion of PrPC into PrPSc after infection with BSE prions. However, Tg(PrPΔOR)/Prnp0/0 mice remained susceptible to RML and 22L scrapie prions, developing the disease without elongated incubation times after infection with RML and 22L prions. PrPScΔOR accumulated only slightly less in the brains of RML- or 22L-infected Tg(PrPΔOR)/Prnp0/0 mice than PrPSc in control wild-type mice. Taken together, these results indicate that the OR region of PrPC could play a differential role in the pathogenesis of BSE prions and RML or 22L scrapie prions.
IMPORTANCE
Structure-function relationship studies of PrPC conformational conversion into PrPSc are worthwhile to understand the mechanism of the conversion of PrPC into PrPSc. We show here that, by inoculating the three different prion strains of RML, 22L and BSE prions, into Tg(PrP∆OR)/Prnp0/0 mice, the OR region could play a differential role in the conversion of PrPC into PrPSc after infection with RML or 22L scrapie prions and BSE prions. PrPΔOR was efficiently converted into PrPScΔOR after infection with RML and 22L prions. However, the conversion of PrPΔOR into PrPScΔOR was markedly delayed after infection with BSE prions. Further investigation into the role of the OR region in the conversion of PrPC into PrPSc after infection with BSE prions might be helpful for understanding the pathogenesis of BSE prions.
Journal Title
Journal of Virology
ISSN
0022538X
10985514
NCID
AA00708779
AA12024806
Publisher
American Society for Microbiology
Volume
92
Issue
1
Start Page
e01368-17
Published Date
2017-10-18
Rights
Copyright © 2017 American Society for Microbiology
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Author
departments
Institute of Advanced Medical Sciences