Prion type-dependent deposition of PRNP allelic products in heterozygous sheep

J.P.M. Langeveld*, J.G. Jacobs, N. Hunter, L.J.M. van Keulen, F. Lantier, F.G. van Zijderveld, A. Bossers

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

Susceptibility or resistance to prion infection in humans and animals depends on single prion protein (PrP) amino acid substitutions in the host, but the agent's modulating role has not been well investigated. Compared to disease incubation times in wild-type homozygous ARQ/ARQ (where each triplet represents the amino acids at codons 136, 154, and 171, respectively) sheep, scrapie susceptibility is reduced to near resistance in ARR/ARR animals while it is strongly enhanced in VRQ/VRQ carriers. Heterozygous ARR/VRQ animals exhibit delayed incubation periods. In bovine spongiform encephalopathy (BSE) infection, the polymorphism effect is quite different although the ARR allotype remains the least susceptible. In this study, PrP allotype composition in protease-resistant prion protein (PrPres) from brain of heterozygous ARR/ VRQ scrapie-infected sheep was compared with that of BSE-infected sheep with a similar genotype. A triplex Western blotting technique was used to estimate the two allotype PrP fractions in PrPres material from BSE-infected ARR/VRQ sheep. PrPres in BSE contained equimolar amounts of VRQ- and ARR-PrP, which contrasts with the excess (>95%) VRQPrP fraction found in PrP in scrapie. This is evidence that transmissible spongiform encephalopathy (TSE) agent properties alone, perhaps structural aspects of prions (such as PrP amino acid sequence variants and PrP conformational state), determine the polymorphic dependence of the PrPres accumulation process in prion formation as well as the disease-associated phenotypic expressions in the host.

Original languageEnglish
Pages (from-to)805-812
JournalJournal of Virology
Volume90
Issue number2
DOIs
Publication statusPublished - 2016

Fingerprint

Prions
prions
Sheep
sheep
Bovine Spongiform Encephalopathy
Scrapie
bovine spongiform encephalopathy
scrapie
Prion Proteins
Prion Diseases
Amino Acid Substitution
Infection
animals
Codon
prion diseases
protein composition
Amino Acid Sequence
amino acid substitution
Peptide Hydrolases
codons

Cite this

Langeveld, J.P.M. ; Jacobs, J.G. ; Hunter, N. ; van Keulen, L.J.M. ; Lantier, F. ; van Zijderveld, F.G. ; Bossers, A. / Prion type-dependent deposition of PRNP allelic products in heterozygous sheep. In: Journal of Virology. 2016 ; Vol. 90, No. 2. pp. 805-812.
@article{1b37dd604a1541abb594f6128fdc5cde,
title = "Prion type-dependent deposition of PRNP allelic products in heterozygous sheep",
abstract = "Susceptibility or resistance to prion infection in humans and animals depends on single prion protein (PrP) amino acid substitutions in the host, but the agent's modulating role has not been well investigated. Compared to disease incubation times in wild-type homozygous ARQ/ARQ (where each triplet represents the amino acids at codons 136, 154, and 171, respectively) sheep, scrapie susceptibility is reduced to near resistance in ARR/ARR animals while it is strongly enhanced in VRQ/VRQ carriers. Heterozygous ARR/VRQ animals exhibit delayed incubation periods. In bovine spongiform encephalopathy (BSE) infection, the polymorphism effect is quite different although the ARR allotype remains the least susceptible. In this study, PrP allotype composition in protease-resistant prion protein (PrPres) from brain of heterozygous ARR/ VRQ scrapie-infected sheep was compared with that of BSE-infected sheep with a similar genotype. A triplex Western blotting technique was used to estimate the two allotype PrP fractions in PrPres material from BSE-infected ARR/VRQ sheep. PrPres in BSE contained equimolar amounts of VRQ- and ARR-PrP, which contrasts with the excess (>95{\%}) VRQPrP fraction found in PrP in scrapie. This is evidence that transmissible spongiform encephalopathy (TSE) agent properties alone, perhaps structural aspects of prions (such as PrP amino acid sequence variants and PrP conformational state), determine the polymorphic dependence of the PrPres accumulation process in prion formation as well as the disease-associated phenotypic expressions in the host.",
author = "J.P.M. Langeveld and J.G. Jacobs and N. Hunter and {van Keulen}, L.J.M. and F. Lantier and {van Zijderveld}, F.G. and A. Bossers",
year = "2016",
doi = "10.1128/JVI.02316-15",
language = "English",
volume = "90",
pages = "805--812",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "2",

}

Langeveld, JPM, Jacobs, JG, Hunter, N, van Keulen, LJM, Lantier, F, van Zijderveld, FG & Bossers, A 2016, 'Prion type-dependent deposition of PRNP allelic products in heterozygous sheep', Journal of Virology, vol. 90, no. 2, pp. 805-812. https://doi.org/10.1128/JVI.02316-15

Prion type-dependent deposition of PRNP allelic products in heterozygous sheep. / Langeveld, J.P.M.; Jacobs, J.G.; Hunter, N.; van Keulen, L.J.M.; Lantier, F.; van Zijderveld, F.G.; Bossers, A.

In: Journal of Virology, Vol. 90, No. 2, 2016, p. 805-812.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Prion type-dependent deposition of PRNP allelic products in heterozygous sheep

AU - Langeveld, J.P.M.

AU - Jacobs, J.G.

AU - Hunter, N.

AU - van Keulen, L.J.M.

AU - Lantier, F.

AU - van Zijderveld, F.G.

AU - Bossers, A.

PY - 2016

Y1 - 2016

N2 - Susceptibility or resistance to prion infection in humans and animals depends on single prion protein (PrP) amino acid substitutions in the host, but the agent's modulating role has not been well investigated. Compared to disease incubation times in wild-type homozygous ARQ/ARQ (where each triplet represents the amino acids at codons 136, 154, and 171, respectively) sheep, scrapie susceptibility is reduced to near resistance in ARR/ARR animals while it is strongly enhanced in VRQ/VRQ carriers. Heterozygous ARR/VRQ animals exhibit delayed incubation periods. In bovine spongiform encephalopathy (BSE) infection, the polymorphism effect is quite different although the ARR allotype remains the least susceptible. In this study, PrP allotype composition in protease-resistant prion protein (PrPres) from brain of heterozygous ARR/ VRQ scrapie-infected sheep was compared with that of BSE-infected sheep with a similar genotype. A triplex Western blotting technique was used to estimate the two allotype PrP fractions in PrPres material from BSE-infected ARR/VRQ sheep. PrPres in BSE contained equimolar amounts of VRQ- and ARR-PrP, which contrasts with the excess (>95%) VRQPrP fraction found in PrP in scrapie. This is evidence that transmissible spongiform encephalopathy (TSE) agent properties alone, perhaps structural aspects of prions (such as PrP amino acid sequence variants and PrP conformational state), determine the polymorphic dependence of the PrPres accumulation process in prion formation as well as the disease-associated phenotypic expressions in the host.

AB - Susceptibility or resistance to prion infection in humans and animals depends on single prion protein (PrP) amino acid substitutions in the host, but the agent's modulating role has not been well investigated. Compared to disease incubation times in wild-type homozygous ARQ/ARQ (where each triplet represents the amino acids at codons 136, 154, and 171, respectively) sheep, scrapie susceptibility is reduced to near resistance in ARR/ARR animals while it is strongly enhanced in VRQ/VRQ carriers. Heterozygous ARR/VRQ animals exhibit delayed incubation periods. In bovine spongiform encephalopathy (BSE) infection, the polymorphism effect is quite different although the ARR allotype remains the least susceptible. In this study, PrP allotype composition in protease-resistant prion protein (PrPres) from brain of heterozygous ARR/ VRQ scrapie-infected sheep was compared with that of BSE-infected sheep with a similar genotype. A triplex Western blotting technique was used to estimate the two allotype PrP fractions in PrPres material from BSE-infected ARR/VRQ sheep. PrPres in BSE contained equimolar amounts of VRQ- and ARR-PrP, which contrasts with the excess (>95%) VRQPrP fraction found in PrP in scrapie. This is evidence that transmissible spongiform encephalopathy (TSE) agent properties alone, perhaps structural aspects of prions (such as PrP amino acid sequence variants and PrP conformational state), determine the polymorphic dependence of the PrPres accumulation process in prion formation as well as the disease-associated phenotypic expressions in the host.

U2 - 10.1128/JVI.02316-15

DO - 10.1128/JVI.02316-15

M3 - Article

VL - 90

SP - 805

EP - 812

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 2

ER -