Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties

Abigail B. Diack; Diane L. Ritchie; Alexander H. Peden; Deborah Brown; Aileen Boyle; Laura Morabito; David Maclennan; Paul Burgoyne; Casper Jansen; Richard S. Knight; Pedro Piccardo; James W. Ironside; Jean C. Manson

doi:10.3201/eid2012.140214

Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties

Abigail B. Diack, Diane L. Ritchie, Alexander H. Peden, Deborah Brown, Aileen Boyle, Laura Morabito, David Maclennan, Paul Burgoyne, Casper Jansen, Richard S. Knight, Pedro Piccardo, James W. Ironside, Jean C. Manson

Research output: Contribution to journal › Article › peer-review

Abstract

Variably protease-sensitive prionopathy (VPSPr) can occur in persons of all codon 129 genotypes in the human prion protein gene (PRNP) and is characterized by a unique biochemical profile when compared with other human prion diseases. We investigated transmission properties of VPSPr by inoculating transgenic mice expressing human PRNP with brain tissue from 2 persons with the valine-homozygous (VV) and 1 with the heterozygous methionine/valine codon 129 genotype. No clinical signs or vacuolar pathology were observed in any inoculated mice. Small deposits of prion protein accumulated in the brains of inoculated mice after challenge with brain material from VV VPSPr patients. Some of these deposits resembled microplaques that occur in the brains of VPSPr patients. Comparison of these transmission properties with those of sporadic Creutzfeldt-Jakob disease in the same lines of mice indicated that VPSPr has distinct biological properties. Moreover, we established that VPSPr has limited potential for human-to-human transmission.

Original language	English
Pages (from-to)	1969-1979
Number of pages	11
Journal	Emerging Infectious Diseases
Volume	20
Issue number	12
DOIs	https://doi.org/10.3201/eid2012.140214
Publication status	Published - 1 Jan 2014

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10.3201/eid2012.140214

Variably Protease-Sensitive Prionopathy, a Unique Prion Variant with Inefficient Transmission Properties
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1 Active

Brain Bank
Smith, C.
MRC
14/06/10 → 31/10/21
Project: Research

Abigail Diack
- abigail.diack@roslin.ed.ac.uk
- Royal (Dick) School of Veterinary Studies - Roslin Research Fellow
Person: Academic: Research Active
Richard Knight
- Centre for Clinical Brain Sciences
- Edinburgh Neuroscience
- Deanery of Clinical Sciences - Professorial Fellow
Person: Academic: Research Active
Jean Manson
- Deanery of Clinical Sciences - Professorial Fellow
- Centre for Clinical Brain Sciences
Person: Academic: Research Active

Cite this

Diack, A. B., Ritchie, D. L., Peden, A. H., Brown, D., Boyle, A., Morabito, L., Maclennan, D., Burgoyne, P., Jansen, C., Knight, R. S., Piccardo, P., Ironside, J. W., & Manson, J. C. (2014). Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties. Emerging Infectious Diseases, 20(12), 1969-1979. https://doi.org/10.3201/eid2012.140214

Diack, Abigail B. ; Ritchie, Diane L. ; Peden, Alexander H. ; Brown, Deborah ; Boyle, Aileen ; Morabito, Laura ; Maclennan, David ; Burgoyne, Paul ; Jansen, Casper ; Knight, Richard S. ; Piccardo, Pedro ; Ironside, James W. ; Manson, Jean C. / Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties. In: Emerging Infectious Diseases. 2014 ; Vol. 20, No. 12. pp. 1969-1979.

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title = "Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties",

abstract = "Variably protease-sensitive prionopathy (VPSPr) can occur in persons of all codon 129 genotypes in the human prion protein gene (PRNP) and is characterized by a unique biochemical profile when compared with other human prion diseases. We investigated transmission properties of VPSPr by inoculating transgenic mice expressing human PRNP with brain tissue from 2 persons with the valine-homozygous (VV) and 1 with the heterozygous methionine/valine codon 129 genotype. No clinical signs or vacuolar pathology were observed in any inoculated mice. Small deposits of prion protein accumulated in the brains of inoculated mice after challenge with brain material from VV VPSPr patients. Some of these deposits resembled microplaques that occur in the brains of VPSPr patients. Comparison of these transmission properties with those of sporadic Creutzfeldt-Jakob disease in the same lines of mice indicated that VPSPr has distinct biological properties. Moreover, we established that VPSPr has limited potential for human-to-human transmission.",

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doi = "10.3201/eid2012.140214",

language = "English",

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Diack, AB , Ritchie, DL , Peden, AH, Brown, D, Boyle, A, Morabito, L, Maclennan, D, Burgoyne, P, Jansen, C, Knight, RS, Piccardo, P, Ironside, JW & Manson, JC 2014, 'Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties', Emerging Infectious Diseases, vol. 20, no. 12, pp. 1969-1979. https://doi.org/10.3201/eid2012.140214

Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties. / Diack, Abigail B.; Ritchie, Diane L.; Peden, Alexander H.; Brown, Deborah; Boyle, Aileen; Morabito, Laura; Maclennan, David; Burgoyne, Paul; Jansen, Casper; Knight, Richard S.; Piccardo, Pedro; Ironside, James W.; Manson, Jean C.

In: Emerging Infectious Diseases, Vol. 20, No. 12, 01.01.2014, p. 1969-1979.

Research output: Contribution to journal › Article › peer-review

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AU - Diack, Abigail B.

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AU - Peden, Alexander H.

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AU - Boyle, Aileen

AU - Morabito, Laura

AU - Maclennan, David

AU - Burgoyne, Paul

AU - Jansen, Casper

AU - Knight, Richard S.

AU - Piccardo, Pedro

AU - Ironside, James W.

AU - Manson, Jean C.

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AB - Variably protease-sensitive prionopathy (VPSPr) can occur in persons of all codon 129 genotypes in the human prion protein gene (PRNP) and is characterized by a unique biochemical profile when compared with other human prion diseases. We investigated transmission properties of VPSPr by inoculating transgenic mice expressing human PRNP with brain tissue from 2 persons with the valine-homozygous (VV) and 1 with the heterozygous methionine/valine codon 129 genotype. No clinical signs or vacuolar pathology were observed in any inoculated mice. Small deposits of prion protein accumulated in the brains of inoculated mice after challenge with brain material from VV VPSPr patients. Some of these deposits resembled microplaques that occur in the brains of VPSPr patients. Comparison of these transmission properties with those of sporadic Creutzfeldt-Jakob disease in the same lines of mice indicated that VPSPr has distinct biological properties. Moreover, we established that VPSPr has limited potential for human-to-human transmission.

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JO - Emerging Infectious Diseases

JF - Emerging Infectious Diseases

SN - 1080-6040

IS - 12

ER -

Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties

Abstract

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Brain Bank

Abigail Diack

Richard Knight

Jean Manson

Cite this