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Variably Protease-Sensitive Prionopathy,a Unique Prion Variant with Inefficient Transmission Properties |
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| Authors: | 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 |
| Affiliation: | The Roslin Institute, University of Edinburgh, Easter Bush, Scotland, UK (A.B. Diack, D. Brown, A, Boyle, L. Morabito, D. Maclennan, P. Burgoyne, J.C. Manson); ;School of Clinical Sciences, University of Edinburgh, Edinburgh, Scotland, UK (D.L. Ritchie, A.H. Peden, R.S. Knight, J.W. Ironside); ;Food and Drug Administration, Rockville, Maryland, USA (P. Piccardo); ;University Medical Centre Utrecht, Utrecht, the Netherlands (C. Jansen) |
| 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. |
| Keywords: | prion variably protease-sensitive prionopathy VPSPr sporadic Creutzfeldt-Jakob disease sCJD transmissible spongiform encephalopathy TSE prion protein human prion disease human-to-human transmission prions and related diseases |