Prion Infectivity and PrPBSE in the Peripheral and Central Nervous System of Cattle 8 Months Post Oral BSE Challenge.

Ivett Ackermann,Olanrewaju I Fatola,Martin H Groschup,Anne Balkema-Buschmann,Reiner Ulrich,Markus Keller,Kerstin Tauscher,James C Shawulu,Stefanie Czub,Mark Arnold

doi:10.3390/ijms222111310

Abstract

After oral exposure of cattle with classical bovine spongiform encephalopathy (C-BSE), the infectious agent ascends from the gut to the central nervous system (CNS) primarily via the autonomic nervous system. However, the timeline of this progression has thus far remained widely undetermined. Previous studies were focused on later time points after oral exposure of animals that were already 4 to 6 months old when challenged. In contrast, in this present study, we have orally inoculated 4 to 6 weeks old unweaned calves with high doses of BSE to identify any possible BSE infectivity and/or PrPBSE in peripheral nervous tissues during the first eight months post-inoculation (mpi). For the detection of BSE infectivity, we used a bovine PrP transgenic mouse bioassay, while PrPBSE depositions were analyzed by immunohistochemistry (IHC) and by protein misfolding cyclic amplification (PMCA). We were able to show that as early as 8 mpi the thoracic spinal cord as well as the parasympathetic nodal ganglion of these animals contained PrPBSE and BSE infectivity. This shows that the centripetal prion spread starts early after challenge at least in this age group, which represents an essential piece of information for the risk assessments for food, feed, and pharmaceutical products produced from young calves.

Highlights

Classical bovine spongiform encephalopathy (C-BSE) is a fatal neurodegenerative prion disease of cattle
We aimed at expanding the currently still incomplete data regarding the early C-BSE pathogenesis, especially in young cattle, by analyzing peripheral nerves and ganglia as well as central nervous tissues sampled from calves at short time points between 1 week and 8 months after oral challenge
We have reported that young unweaned calves were susceptible to an infection with a high BSE dose, as indicated by significant amounts of PrPBSE and high infectivity loads in some of the analyzed ileal Peyer’s patch (IPP) samples from 2 mpi on [8]

Summary

Introduction

Classical bovine spongiform encephalopathy (C-BSE) is a fatal neurodegenerative prion disease of cattle. Other prion diseases or transmissible spongiform encephalopathies (TSEs) include Creutzfeldt–Jakob disease (CJD) in humans, scrapie in small ruminants, as well as chronic wasting disease (CWD) in cervids. These disorders are caused by the conversion of a host-encoded cellular membrane-bound glycoprotein (PrPC) into its abnormal isoform, the pathological prion protein (PrPTSE) [1]. The SRM list of bovines born in EU member states with negligible BSE risk-as defined in Regulation (EC) No 999/2001 (consolidated version as of 11.2020)-includes the skull (excluding the mandible) with brain and eyes as well as the spinal cord of animals over 12 months of age. For cattle of all ages originating from countries with a controlled or undetermined BSE risk, the last 4 meters of the small intestine, tonsils, caecum, mesentery, including mesenteric ganglion complex, nerves and fat as well as parts of the vertebral column (including dorsal root ganglia) of animals over 30 months have to be removed and destroyed

Methods

Discussion

Conclusion