Transmission Characteristics of Variably Protease-sensitive Prionopathy

Overview

Journal Emerg Infect Dis

Specialty Infectious Diseases

Date 2014 Nov 25

PMID 25418590

Citations 27

Authors

Silvio Notari

Xiangzhu Xiao

Juan Carlos Espinosa

Yvonne Cohen

Liuting Qing

Patricia Aguilar-Calvo

Diane Kofskey

Ignazio Cali

Laura Cracco

Qingzhong Kong

Juan Maria Torres

Wenquan Zou

Pierluigi Gambetti

Affiliations

Soon will be listed here.

Abstract

Variably protease-sensitive prionopathy (VPSPr), a recently identified and seemingly sporadic human prion disease, is distinct from Creutzfeldt-Jakob disease (CJD) but shares features of Gerstmann-Sträussler-Scheinker disease (GSS). However, contrary to exclusively inherited GSS, no prion protein (PrP) gene variations have been detected in VPSPr, suggesting that VPSPr might be the long-sought sporadic form of GSS. The VPSPr atypical features raised the issue of transmissibility, a prototypical property of prion diseases. We inoculated VPSPr brain homogenate into transgenic mice expressing various levels of human PrP (PrPC). On first passage, 54% of challenged mice showed histopathologic lesions, and 34% harbored abnormal PrP similar to that of VPSPr. Surprisingly, no prion disease was detected on second passage. We concluded that VPSPr is transmissible; thus, it is an authentic prion disease. However, we speculate that normal human PrPC is not an efficient conversion substrate (or mouse brain not a favorable environment) and therefore cannot sustain replication beyond the first passage.

Citing Articles

Search for a genetic cause of variably protease-sensitive prionopathy.

Lian Y, Kotobelli K, Hall S, Talkowski M, ODonnell-Luria A, Vallabh S medRxiv. 2024; .

PMID: 39711705 PMC: 11661330. DOI: 10.1101/2024.12.12.24318867.

Characterization of variably protease-sensitive prionopathy by capillary electrophoresis.

Myskiw J, Bailey-Elkin B, Avery K, Barria M, Ritchie D, Cohen M Sci Rep. 2024; 14(1):27867.

PMID: 39537719 PMC: 11561330. DOI: 10.1038/s41598-024-79217-1.

Updated global epidemiology atlas of human prion diseases.

Gao L, Tian T, Xiao K, Chen C, Zhou W, Liang D Front Public Health. 2024; 12:1411489.

PMID: 38939567 PMC: 11208307. DOI: 10.3389/fpubh.2024.1411489.

Efficient transmission of human prion diseases to a glycan-free prion protein-expressing host.

Cracco L, Cali I, Cohen M, Aslam R, Notari S, Kong Q Brain. 2023; 147(4):1539-1552.

PMID: 38000783 PMC: 10994570. DOI: 10.1093/brain/awad399.

A novel subtype of sporadic Creutzfeldt-Jakob disease with PRNP codon 129MM genotype and PrP plaques.

Bayazid R, Orru C, Aslam R, Cohen Y, Silva-Rohwer A, Lee S Acta Neuropathol. 2023; 146(1):121-143.

PMID: 37156880 PMC: 10166463. DOI: 10.1007/s00401-023-02581-1.

References

Padilla D, Beringue V, Espinosa J, Andreoletti O, Jaumain E, Reine F . Sheep and goat BSE propagate more efficiently than cattle BSE in human PrP transgenic mice. PLoS Pathog. 2011; 7(3):e1001319. PMC: 3060172. DOI: 10.1371/journal.ppat.1001319. View

Sandberg M, Al-Doujaily H, Sharps B, Clarke A, Collinge J . Prion propagation and toxicity in vivo occur in two distinct mechanistic phases. Nature. 2011; 470(7335):540-2. DOI: 10.1038/nature09768. View

Makarava N, Kovacs G, Savtchenko R, Alexeeva I, Budka H, Rohwer R . Genesis of mammalian prions: from non-infectious amyloid fibrils to a transmissible prion disease. PLoS Pathog. 2011; 7(12):e1002419. PMC: 3228811. DOI: 10.1371/journal.ppat.1002419. View

Puoti G, Bizzi A, Forloni G, Safar J, Tagliavini F, Gambetti P . Sporadic human prion diseases: molecular insights and diagnosis. Lancet Neurol. 2012; 11(7):618-28. DOI: 10.1016/S1474-4422(12)70063-7. View

Aguzzi A, Falsig J . Prion propagation, toxicity and degradation. Nat Neurosci. 2012; 15(7):936-9. DOI: 10.1038/nn.3120. View

Tamguney G, Giles K, Oehler A, Johnson N, DeArmond S, Prusiner S . Chimeric elk/mouse prion proteins in transgenic mice. J Gen Virol. 2012; 94(Pt 2):443-452. PMC: 3709613. DOI: 10.1099/vir.0.045989-0. View

Xiao X, Yuan J, Haik S, Cali I, Zhan Y, Moudjou M . Glycoform-selective prion formation in sporadic and familial forms of prion disease. PLoS One. 2013; 8(3):e58786. PMC: 3602448. DOI: 10.1371/journal.pone.0058786. View

Asante E, Linehan J, Smidak M, Tomlinson A, Grimshaw A, Jeelani A . Inherited prion disease A117V is not simply a proteinopathy but produces prions transmissible to transgenic mice expressing homologous prion protein. PLoS Pathog. 2013; 9(9):e1003643. PMC: 3784465. DOI: 10.1371/journal.ppat.1003643. View

Pirisinu L, Nonno R, Esposito E, Benestad S, Gambetti P, Agrimi U . Small ruminant nor98 prions share biochemical features with human gerstmann-sträussler-scheinker disease and variably protease-sensitive prionopathy. PLoS One. 2013; 8(6):e66405. PMC: 3691246. DOI: 10.1371/journal.pone.0066405. View

10.

Head M, Yull H, Ritchie D, Langeveld J, Fletcher N, Knight R . Variably protease-sensitive prionopathy in the UK: a retrospective review 1991-2008. Brain. 2013; 136(Pt 4):1102-15. DOI: 10.1093/brain/aws366. View

11.

Piccardo P, King D, Telling G, Manson J, Barron R . Dissociation of prion protein amyloid seeding from transmission of a spongiform encephalopathy. J Virol. 2013; 87(22):12349-56. PMC: 3807897. DOI: 10.1128/JVI.00673-13. View

12.

Prusiner S . Biology and genetics of prions causing neurodegeneration. Annu Rev Genet. 2013; 47:601-23. PMC: 4010318. DOI: 10.1146/annurev-genet-110711-155524. View

13.

Hegde R, Tremblay P, Groth D, DeArmond S, Prusiner S, Lingappa V . Transmissible and genetic prion diseases share a common pathway of neurodegeneration. Nature. 2000; 402(6763):822-6. DOI: 10.1038/45574. View

14.

Race R, Raines A, Raymond G, Caughey B, Chesebro B . Long-term subclinical carrier state precedes scrapie replication and adaptation in a resistant species: analogies to bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease in humans. J Virol. 2001; 75(21):10106-12. PMC: 114584. DOI: 10.1128/JVI.75.21.10106-10112.2001. View

15.

Race R, Meade-White K, Raines A, Raymond G, Caughey B, Chesebro B . Subclinical scrapie infection in a resistant species: persistence, replication, and adaptation of infectivity during four passages. J Infect Dis. 2002; 186 Suppl 2:S166-70. DOI: 10.1086/344267. View

16.

Weissmann C, Flechsig E . PrP knock-out and PrP transgenic mice in prion research. Br Med Bull. 2003; 66:43-60. DOI: 10.1093/bmb/66.1.43. View

17.

Gambetti P, Kong Q, Zou W, Parchi P, Chen S . Sporadic and familial CJD: classification and characterisation. Br Med Bull. 2003; 66:213-39. DOI: 10.1093/bmb/66.1.213. View

18.

Bueler H, Aguzzi A, Sailer A, Greiner R, Autenried P, Aguet M . Mice devoid of PrP are resistant to scrapie. Cell. 1993; 73(7):1339-47. DOI: 10.1016/0092-8674(93)90360-3. View

19.

Sailer A, Bueler H, Fischer M, Aguzzi A, Weissmann C . No propagation of prions in mice devoid of PrP. Cell. 1994; 77(7):967-8. DOI: 10.1016/0092-8674(94)90436-7. View

20.

Fischer M, Rulicke T, Raeber A, Sailer A, Moser M, Oesch B . Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie. EMBO J. 1996; 15(6):1255-64. PMC: 450028. View