Ovine prion protein variant A136R154L168Q171 increases resistance to experimental challenge with bovine spongiform encephalopathy agent

Author:

Goldmann Wilfred1,Houston Fiona2,Stewart Paula1,Perucchini Matteo1,Foster James1,Hunter Nora1

Affiliation:

1. Institute for Animal Health (IAH), Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, UK

2. IAH, Compton Laboratory, Compton, Berkshire RG20 7NN, UK

Abstract

Susceptibility and incubation periods of transmissible spongiform encephalopathies, such as scrapie in sheep, are modulated by the PrP gene. The standard model of association between ovine PrP genetics and classical scrapie susceptibility is based on PrP genotypes with respect to codons 136, 154 and 171, e.g. alanine–arginine–glutamine (ARQ). It is demonstrated here that a proline to leucine substitution in codon 168 of the ovine PrP protein gene is associated with increased resistance to experimental bovine spongiform encephalopathy (BSE) inoculation. The ARL168Q PrP allele was found in heterozygous ARP168Q/ARL168Q sheep that have so far survived intravenous BSE challenge three times longer than BSE-challenged homozygous ARP168Q/ARP168Q sheep, which develop disease in around 700 days. In contrast, the L141F polymorphism does not appear to be associated with susceptibility to intravenous BSE challenge.

Publisher

Microbiology Society

Subject

Virology

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