Acquired transmissibility of sheep-passaged L-type bovine spongiform encephalopathy prion to wild-type mice.

Hiroyuki Okada,Takashi Yokoyama,Kentaro Masujin,Kohtaro Miyazawa

doi:10.1186/s13567-015-0211-2

Hiroyuki Okada, Takashi Yokoyama + Show 2 more

Open Access

https://doi.org/10.1186/s13567-015-0211-2

Copy DOI

Abstract

L-type bovine spongiform encephalopathy (L-BSE) is an atypical form of BSE that is transmissible to cattle and several lines of prion protein (PrP) transgenic mice, but not to wild-type mice. In this study, we examined the transmissibility of sheep-passaged L-BSE prions to wild-type mice. Disease-associated prion protein (PrPSc) was detected in the brain and/or lymphoid tissues during the lifespan of mice that were asymptomatic subclinical carriers, indicating that wild-type mice were susceptible to sheep-passaged L-BSE. The morphological characteristics of the PrPSc of sheep-passaged L-BSE included florid plaques that were distributed mainly in the cerebral cortex and hippocampus of subsequent passaged mice. The PrPSc glycoform profiles of wild-type mice infected with sheep-passaged L-BSE were similar to those of the original isolate. The data indicate that sheep-passaged L-BSE has an altered host range and acquired transmissibility to wild-type mice.

Highlights

Bovine spongiform encephalopathy (BSE) was originally thought to be caused by a single prion strain, based on analysis of its biological and biochemical characteristics
First and second passage of L-type bovine spongiform encephalopathy (L-BSE)/sheep to wild-type mice The first-passaged mice with L-BSE/sheep showed no clinical signs of the disease and were sacrificed at the end of their lives, or at an earlier stage of deterioration in accordance with welfare concerns relating to animal experiments, during the period between 172 and 1012 days post-inoculation (Table 1)
A PrPSc signal was detected by Western Blotting (WB), IHC, or both techniques in the brain from 1 case at 710 dpi, and in lymphoid tissues from 9 of 15 mice after 200 dpi after the first passage

Summary

Introduction

Bovine spongiform encephalopathy (BSE) was originally thought to be caused by a single prion strain, based on analysis of its biological and biochemical characteristics. Atypical BSE is classified into two groups depending on whether the proteinase K (PK)-resistant abnormal, disease-associated form of the prion protein (PrPSc) has higher (H-BSE) or lower (LBSE) molecular mass than that of classical (C-) BSE [1]. L-BSE prions have shown transmissibility by intracerebral challenge to cattle [3,4,5,6]; bovinized [7,8,9,10], ovinized [7,10,11], and humanized prion protein (PrP) transgenic mice [12]; Syrian hamsters [13,14], and non-human primates [15] with a shorter incubation period than C-BSE.

Methods

Results

Conclusion