Prion Protein Devoid of the Octapeptide Repeat Region Delays Bovine Spongiform Encephalopathy Pathogenesis in Mice
| العنوان: | Prion Protein Devoid of the Octapeptide Repeat Region Delays Bovine Spongiform Encephalopathy Pathogenesis in Mice |
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| المؤلفون: | Hironori Miyata, Nandita Rani Das, Gen Kondoh, Hitomi Watanabe, Keiji Uchiyama, Suehiro Sakaguchi, Hideyuki Hara, Tatenobu Yoshimochi, Takashi Yokoyama, Junji Chida |
| المصدر: | Journal of Virology. 92 |
| بيانات النشر: | American Society for Microbiology, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Gene isoform, Prions, animal diseases, Transgene, Bovine spongiform encephalopathy, Immunology, Encephalopathy, Mice, Transgenic, Scrapie, Biology, Microbiology, Prion Diseases, Pathogenesis, Mice, 03 medical and health sciences, Virology, mental disorders, medicine, Animals, Humans, PrPC Proteins, Prion protein, Sequence Deletion, Brain, medicine.disease, nervous system diseases, Encephalopathy, Bovine Spongiform, 030104 developmental biology, Reduced susceptibility, Insect Science, Cattle, Disease Susceptibility, Oligopeptides |
| الوصف: | Conformational conversion of the cellular isoform of prion protein, PrP C , into the abnormally folded, amyloidogenic isoform, PrP Sc , 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 PrP C into PrP Sc 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)/ Prnp 0 / 0 mice, did not show reduced susceptibility to RML scrapie prions, with abundant accumulation of PrP Sc ΔOR in their brains. We show here that Tg(PrPΔOR)/ Prnp 0 / 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 PrP Sc ΔOR was markedly delayed in their brains. These results suggest that the OR region may have a crucial role in the conversion of PrP C into PrP Sc after infection with BSE prions. However, Tg(PrPΔOR)/ Prnp 0 / 0 mice remained susceptible to RML and 22L scrapie prions, developing the disease without elongated incubation times after infection with RML and 22L prions. PrP Sc ΔOR accumulated only slightly less in the brains of RML- or 22L-infected Tg(PrPΔOR)/ Prnp 0 / 0 mice than PrP Sc in control wild-type mice. Taken together, these results indicate that the OR region of PrP C could play a differential role in the pathogenesis of BSE prions and RML or 22L scrapie prions. IMPORTANCE Structure-function relationship studies of PrP C conformational conversion into PrP Sc are worthwhile to understand the mechanism of the conversion of PrP C into PrP Sc . We show here that, by inoculating Tg(PrPΔOR)/ Prnp 0 / 0 mice with the three different strains of RML, 22L, and BSE prions, the OR region could play a differential role in the conversion of PrP C into PrP Sc after infection with RML or 22L scrapie prions and BSE prions. PrPΔOR was efficiently converted into PrP Sc ΔOR after infection with RML and 22L prions. However, the conversion of PrPΔOR into PrP Sc ΔOR was markedly delayed after infection with BSE prions. Further investigation into the role of the OR region in the conversion of PrP C into PrP Sc after infection with BSE prions might be helpful for understanding the pathogenesis of BSE prions. |
| تدمد: | 1098-5514 0022-538X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e002f3371e9a0e59113dc9430ed15c06Test https://doi.org/10.1128/jvi.01368-17Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e002f3371e9a0e59113dc9430ed15c06 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985514 0022538X |
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