Guinea pig prion protein supports rapid propagation of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease prions

Joel C. Watts, Kurt Giles, Daniel J. Saltzberg, Brittany Dugger, Smita Patel, Abby Oehler, Sumita Bhardwaj, Andrej Sali, Stanley B. Prusiner

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The biochemical and neuropathological properties of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) prions are faithfully maintained upon transmission to guinea pigs. However, primary and secondary transmissions of BSE and vCJD in guinea pigs result in long incubation periods of ~450 and ~350 days, respectively. To determine if the incubation periods of BSE and vCJD prions could be shortened, we generated transgenic (Tg) mice expressing guinea pig prion protein (GPPrP). Inoculation of Tg(GPPrP) mice with BSE and vCJD prions resulted in mean incubation periods of 210 and 199 days, respectively, which shortened to 137 and 122 days upon serial transmission. In contrast, three different isolates of sporadic CJD prions failed to transmit disease to Tg(GPPrP) mice. Many of the strain-specified biochemical and neuropathological properties of BSE and vCJD prions, including the presence of type 2 protease-resistant PrPSc, were preserved upon propagation in Tg(GPPrP) mice. Structural modeling revealed that two residues near the N-terminal region of α-helix 1 in GPPrP might mediate its susceptibility to BSE and vCJD prions. Our results demonstrate that expression of GPPrP in Tg mice supports the rapid propagation of BSE and vCJD prions and suggest that Tg(GPPrP) mice may serve as a useful paradigm for bioassaying these prion isolates.

Original languageEnglish (US)
Pages (from-to)9558-9569
Number of pages12
JournalJournal of Virology
Volume90
Issue number21
DOIs
StatePublished - Jan 1 2016

Fingerprint

Creutzfeldt-Jakob Syndrome
Bovine Spongiform Encephalopathy
bovine spongiform encephalopathy
Prions
prions
guinea pigs
Guinea Pigs
genetically modified organisms
mice
Transgenic Mice
Prion Proteins
primary transmission
secondary transmission
PrPSc proteins
Peptide Hydrolases

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Guinea pig prion protein supports rapid propagation of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease prions. / Watts, Joel C.; Giles, Kurt; Saltzberg, Daniel J.; Dugger, Brittany; Patel, Smita; Oehler, Abby; Bhardwaj, Sumita; Sali, Andrej; Prusiner, Stanley B.

In: Journal of Virology, Vol. 90, No. 21, 01.01.2016, p. 9558-9569.

Research output: Contribution to journalArticle

Watts, JC, Giles, K, Saltzberg, DJ, Dugger, B, Patel, S, Oehler, A, Bhardwaj, S, Sali, A & Prusiner, SB 2016, 'Guinea pig prion protein supports rapid propagation of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease prions', Journal of Virology, vol. 90, no. 21, pp. 9558-9569. https://doi.org/10.1128/JVI.01106-16
Watts, Joel C. ; Giles, Kurt ; Saltzberg, Daniel J. ; Dugger, Brittany ; Patel, Smita ; Oehler, Abby ; Bhardwaj, Sumita ; Sali, Andrej ; Prusiner, Stanley B. / Guinea pig prion protein supports rapid propagation of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease prions. In: Journal of Virology. 2016 ; Vol. 90, No. 21. pp. 9558-9569.
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