Emergence of a novel bovine spongiform encephalopathy (BSE) prion from an atypical H-type BSE.

Kentaro Masujin,Yuichi Murayama,Yoshifumi Iwamaru,Takashi Yokoyama,Yuichi Matsuura,Kohtaro Miyazawa,Morikazu Imamura,Hiroyuki Okada

doi:10.1038/srep22753

Abstract

The H-type of atypical bovine spongiform encephalopathy (H-BSE) was serially passaged in bovinized transgenic (TgBoPrP) mice. At the fourth passage, most challenged mice showed a typical H-BSE phenotype with incubation periods of 223 ± 7.8 days. However, a different phenotype of BSE prion with shorter incubation periods of 109 ± 4 days emerged in a minor subset of the inoculated mice. The latter showed distinct clinical signs, brain pathology, and abnormal prion protein profiles as compared to H-BSE and other known BSE strains in mice. This novel prion was transmitted intracerebrally to cattle, with incubation periods of 14.8 ± 1.5 months, with phenotypes that differed from those of other bovine prion strains. These data suggest that intraspecies transmission of H-BSE in cattle allows the emergence of a novel BSE strain. Therefore, the continuation of feed ban programs may be necessary to exclude the recycling of H-BSE prions, which appear to arise spontaneously, in livestock. Such measures should help to reduce the risks from both novel and known strains of BSE.

Highlights

Prions cause transmissible spongiform encephalopathies (TSEs), which are characterized by a spongiform change in the central nervous system and the accumulation of an abnormal prion protein (PrPSc)
Our previous reports have revealed the usefulness of TgBoPrP mice for characterizing Bovine spongiform encephalopathy (BSE) prions[16,21,22]
We have previously performed several transmission experiments of sheep scrapie to TgBoPrP mice, but their incubation periods were over 170 days[23], and we have not observed any prions with ~90-day incubation periods in these mice

Summary

Introduction

Prions cause transmissible spongiform encephalopathies (TSEs), which are characterized by a spongiform change in the central nervous system and the accumulation of an abnormal prion protein (PrPSc). Western blot analysis with monoclonal antibody (mAb) 6H4 revealed that the molecular mass of proteinase K (PK) digested PrPSc (PrPcore) of BSE-SW was lower than that of H-BSE, but similar to C-BSE (Fig. 1b). The degree of brain vacuolation and neuroanatomical distribution patterns of PrPSc in TgBoPrP mice with BSE-SW were different from H-BSE and C-BSE (Fig. 2).

Results

Conclusion