Alteration of the chronic wasting disease species barrier by in vitro prion amplification

Timothy D. Kurt, Davis M. Seelig, Jay R. Schneider, Christopher J. Johnson, Glenn C. Telling, Dennis M. Heisey, Edward A. Hoover

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of cervids now detected in 19 states of the United States, three Canadian provinces, and South Korea. Whether noncervid species can be infected by CWD and thereby serve as reservoirs for the infection is not known. To investigate this issue, we previously used serial protein misfolding cyclic amplification (sPMCA) to demonstrate that CWD prions can amplify in brain homogenates from several species sympatric with cervids, including prairie voles (Microtus ochrogaster) and field mice (Peromyscus spp.). Here, we show that prairie voles are susceptible to mule deer CWD prions in vivo and that sPMCA amplification of CWD prions in vole brain enhances the infectivity of CWD for this species. Prairie voles inoculated with sPMCA products developed clinical signs of TSE disease approximately 300 days prior to, and more consistently than, those inoculated with CWD prions from deer brain. Moreover, the deposition patterns and biochemical properties of protease-resistant form of PrP (Pr PRES) in the brains of affected voles differed from those in cervidized transgenic (CerPrP) mice infected with CWD. In addition, voles inoculated orally with sPMCA products developed clinical signs of TSE and were positive for PrPRES deposition, whereas those inoculated orally with deer-origin CWD prions did not. These results demonstrate that transspecies sPMCA of CWD prions can enhance the infectivity and adapt the host range of CWD prions and thereby may be useful to assess determinants of prion species barriers.

Original languageEnglish (US)
Pages (from-to)8528-8537
Number of pages10
JournalJournal of virology
Volume85
Issue number17
DOIs
StatePublished - Sep 1 2011

Fingerprint

Chronic Wasting Disease
chronic wasting disease
Prions
prions
Arvicolinae
Microtus ochrogaster
Prion Diseases
Deer
prion diseases
brain
Brain
Proteins
proteins
deer
In Vitro Techniques
pathogenicity
Peromyscus
Sympatry
Republic of Korea
Odocoileus hemionus

Cite this

Kurt, T. D., Seelig, D. M., Schneider, J. R., Johnson, C. J., Telling, G. C., Heisey, D. M., & Hoover, E. A. (2011). Alteration of the chronic wasting disease species barrier by in vitro prion amplification. Journal of virology, 85(17), 8528-8537. https://doi.org/10.1128/JVI.00809-11

Alteration of the chronic wasting disease species barrier by in vitro prion amplification. / Kurt, Timothy D.; Seelig, Davis M.; Schneider, Jay R.; Johnson, Christopher J.; Telling, Glenn C.; Heisey, Dennis M.; Hoover, Edward A.

In: Journal of virology, Vol. 85, No. 17, 01.09.2011, p. 8528-8537.

Research output: Contribution to journalArticle

Kurt, TD, Seelig, DM, Schneider, JR, Johnson, CJ, Telling, GC, Heisey, DM & Hoover, EA 2011, 'Alteration of the chronic wasting disease species barrier by in vitro prion amplification', Journal of virology, vol. 85, no. 17, pp. 8528-8537. https://doi.org/10.1128/JVI.00809-11
Kurt, Timothy D. ; Seelig, Davis M. ; Schneider, Jay R. ; Johnson, Christopher J. ; Telling, Glenn C. ; Heisey, Dennis M. ; Hoover, Edward A. / Alteration of the chronic wasting disease species barrier by in vitro prion amplification. In: Journal of virology. 2011 ; Vol. 85, No. 17. pp. 8528-8537.
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