Conserved Properties of Human and Bovine Prion Strains on Transmission to Guinea Pigs

Overview

Journal Lab Invest

Specialty Pathology

Date 2011 Jul 6

PMID 21727894

Citations 7

Authors

Jiri G Safar

Kurt Giles

Pierre Lessard

Frederic Letessier

Smita Patel

Ana Serban

Stephen J DeArmond

Stanley B Prusiner

Affiliations

Soon will be listed here.

Abstract

The first transmissions of human prion diseases to rodents used guinea pigs (Gps, Cavia porcellus). Later, transgenic mice expressing human or chimeric human/mouse PrP replaced Gps, but the small size of the mouse limits some investigations. To investigate the fidelity of strain-specific prion transmission to Gps, we inoculated 'type 1' and 'type 2' prion strains into Gps, and we measured the incubation times and determined the strain-specified size of the unglycosylated, protease-resistant (r) PrP(Sc) fragment. Prions passaged once in Gps from cases of sporadic (s) Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker (GSS) disease caused by the P102L mutation were used, as well as human prions from a variant (v) CJD case, bovine prions from bovine spongiform encephalopathy (BSE) and mouse-passaged scrapie prions. Variant CJD and BSE prions transmitted to all the inoculated Gps with incubation times of 367 ± 4 and 436 ± 28 days, respectively. On second passage in Gps, vCJD and BSE prions caused disease in 287 ± 4 and 310 ± 4 days, whereas sCJD and GSS prions transmitted in 237 ± 4 and 279 ± 19 days, respectively. Although hamster Sc237 prions transmitted to two of three Gps after 574 and 792 days, mouse-passaged RML and 301V prion strains, the latter derived from BSE prions, failed to transmit disease to Gps. Those Gps inoculated with vCJD or BSE prions exhibited 'type 2' unglycosylated, rPrP(Sc) (19 kDa), whereas those receiving sCJD or GSS prions displayed 'type 1' prions (21 kDa), as determined by western blotting. Such strain-specific properties were maintained in Gps as well as mice expressing a chimeric human/mouse transgene. Gps may prove particularly useful in further studies of novel human prions such as those causing vCJD.

Citing Articles

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Hromadkova L, Siddiqi M, Liu H, Safar J Cells. 2022; 11(19).

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Structurally distinct external solvent-exposed domains drive replication of major human prions.

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Guinea Pig Prion Protein Supports Rapid Propagation of Bovine Spongiform Encephalopathy and Variant Creutzfeldt-Jakob Disease Prions.

Watts J, Giles K, Saltzberg D, Dugger B, Patel S, Oehler A J Virol. 2016; 90(21):9558-9569.

PMID: 27440899 PMC: 5068510. DOI: 10.1128/JVI.01106-16.

Human prion protein sequence elements impede cross-species chronic wasting disease transmission.

Kurt T, Jiang L, Fernandez-Borges N, Bett C, Liu J, Yang T J Clin Invest. 2015; 125(4):1485-96.

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Evidence that bank vole PrP is a universal acceptor for prions.

Watts J, Giles K, Patel S, Oehler A, DeArmond S, Prusiner S PLoS Pathog. 2014; 10(4):e1003990.

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