Significant differences in incubation times in sheep infected with bovine spongiform encephalopathy result from variation at codon 141 in the PRNP gene

Tan, B. C., Blanco, A. R. A., Houston, E.F., Stewart, P., Goldmann, W., Gill, A. C., de Wolf, C., Manson, J. C. and McCutcheon, S. (2012) Significant differences in incubation times in sheep infected with bovine spongiform encephalopathy result from variation at codon 141 in the PRNP gene. Journal of General Virology, 93(Pt_12), pp. 2749-2756. (doi: 10.1099/vir.0.039008-0)

Abstract

The susceptibility of sheep to prion infection is linked to variation in the PRNP gene, which encodes the prion protein. Common polymorphisms occur at codons 136, 154 and 171. Sheep which are homozygous for the A₁₃₆R₁₅₄Q₁₇₁ allele are the most susceptible to bovine spongiform encephalopathy (BSE). The effect of other polymorphisms on BSE susceptibility is unknown. We orally infected ARQ/ARQ Cheviot sheep with equal amounts of BSE brain homogenate and a range of incubation periods was observed. When we segregated sheep according to the amino acid (L or F) encoded at codon 141 of the PRNP gene, the shortest incubation period was observed in LL141 sheep, whilst incubation periods in FF₁₄₁ and LF₁₄₁ sheep were significantly longer. No statistically significant differences existed in the expression of total prion protein or the disease-associated isoform in BSE-infected sheep within each genotype subgroup. This suggested that the amino acid encoded at codon 141 probably affects incubation times through direct effects on protein misfolding rates.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Houston, Dr Fiona
• Authors: Tan, B. C., Blanco, A. R. A., Houston, E.F., Stewart, P., Goldmann, W., Gill, A. C., de Wolf, C., Manson, J. C., and McCutcheon, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Journal of General Virology
• Publisher: Society for General Microbiology
• ISSN: 0022-1317
• ISSN (Online): 1465-2099
• Published Online: 12 September 2012
• Copyright Holders: Copyright © 2012 Society for General Microbiology
• First Published: First published in Journal of General Virology 93(12):2749-2756
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher