NR AWFZ
AU Green,K.M.; Browning,S.R.; Seward,T.S.; Green,M.; Hoover,E.A.; Telling,G.C.
TI Interspecies prion transmission is controlled by conformational compatibility between PrPsc and heterotypic PrPc
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Oral sessions ORAL-19
PT Konferenz-Vortrag
AB The threats to humans and livestock from interspecies prion transmission are difficult to assess because the factors controlling this process remain uncertain. To address this we have used transgenic mouse models to understand the roles played by PrP primary structure, prion strains and the species specificity of protein X in controlling interspecies prion infection in the context of cervid transmission barriers. Cervid prions are of particular concern because chronic wasting disease (CWD) of North American and South Korean cervids is the only recognized prion disease of wild animals and its increasing geographic range, contagious nature, and environmental persistence have raised concerns about prion dissemination and the potential for further interspecies transmission. We show that conformational compatibility of PrPsc in a prion strain and PrP primary structure in a new host is the most important determinant of interspecies prion transmission barriers. Although prion strains can acquire totally new host range properties following heterologous conversion of PrPc in a new host, the strain-related biochemical properties of PrPsc may remain relatively stable. We also show that the cervid PrP polymorphism at residue 132, which is equivalent to the human PrP 129 polymorphism, is a crucial determinant of cervid prion transmission and has a profound controlling effect on PrPsc-related prion strain properties. Our transgenic approaches modeling trans-species prion susceptibility in cervids also speak to the possible origins of CWD since cervid transgenic mice are also vulnerable, to varying degrees, to sheep scrapie prions, the degree of susceptibility being strain related. One particularly well-characterized sheep scrapie isolate, SSBP/1, caused disease as efficiently as CWD prions from diseased deer or elk. Finally, while transmissions in transgenic mice based on the protein X model of prion propagation produced chimeric prions, passage of which resulted in novel cervid prions with an extended host range compared to CWD-cervid prions, the unexpected susceptibilities of such mice to CWD and mouse prions are inconsistent with the previously hypothesized role of protein X in prion propagation.
AD K.M. Green: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, Ky, USA; S.R. Browning: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, Ky, USA, present address: Department of Infectiology, Scripps Research Institute, Jupiter, Florida, USA; T.S. Seward: Sanders Brown Center on Aging; M. Green: UK Transgenic Facility, University of Kentucky, Lexington, Ky, USA; E.A. Hoover: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Co, USA; G.C. Telling: Department of Microbiology, Immunology and Molecular Genetics, Sanders Brown Center on Aging, Department of Neurology, University of Kentucky, Lexington, Ky, USA. E-mail: gtell2@uky.edu
SP englisch
PO Italien