NR AXLT
AU Espinosa,J.C.; Andreoletti,O.; Herva,M.E.; Alamillo,E.; Padilla,D.; Lacroux,C.; Groschup,M.H.; Torres,J.M.
TI Elements Modulating Transmission Barrier and Virulence in BSE-Derived Prions
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Oral Abstracts FC2.6
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Vortrag
AB
Background: BSE is considered a promiscuous strain because have been able to infect a wide range of species. Nevertheless, the transmission barrier found for BSE infection in other species is in a broad range from low to high susceptibility depending on the host. When prion species barrier is crossed both biochemical and biological prion strain properties can change as an adaptation to the new species. However, the elements modulating these changes are not well known.
Objectives: This work is addressed to analyse the putative elements modulating the biological, biochemical and histopathological properties of BSE after crossing the transmission barrier in different species.
Methods: A collection of BSE-derived prions having the same strain origin (BSE inoculum) but harbouring different PrPsc amino acid sequences has been generated by intracerebral inoculation in four different mouse lines expressing PrPc from different species (bovine, murine, porcine and ovine). These BSE-derived prions allow analysing those properties associated to the prion strain versus those depending on the PrP amino acid sequence. Biochemical, histopathological and biological properties of the new generated BSE-derived prions have been analysed in comparison to both the original BSE inoculum and others non-related prion strains.
Results: The different BSE-derived prions inoculated in BoPrP-Tg110 showed lack of transmission barrier, independently of the PrPsc amino acid sequence of the inoculum (a marked transmission barrier is present for non-BSE prion strains). BSE-prions generated after passage in mice expressing ARQ-ovine PrP increase its virulence (survival time is shortened). By contrast, the passage of BSE strain in mice expressing murine-PrP decreases its virulence (survival time is lengthened). In both cases, the new biological properties are maintained after subpassage in BoPrP-Tg110.
Discussion: These results indicate that BSE transmission barrier is modulated by strain (conformation-depending) properties rather than by PrP amino acid sequence. Interestingly, passage of BSE strain in host expressing other species PrP modifies its biological properties altering the survival time when analysed in BoPrP-Tg110 mice. These alterations are due to elements included in the PrP amino acid sequence but not to other species-specific factors. These elements are under consideration.
AD J.C. Espinosa, M.E. Herva, E. Alamillo, D. Padilla, J.M. Torres, CISA-INIA, Spain; O. Andréoletti, C. Lacroux, INRA-ENVT, France; M.H. Groschup, FLI-INEID, Germany
SP englisch
PO Schottland