Research Objective:
The diversity of prion strains in Classical scrapie is well known, resulting in different biological behavior and even the potential to cross the human species barrier in relevant animal models has been shown. However, the mechanism controlling prion strain evolution and the factors that determine the zoonotic potential of a prion strain are still unclear. Therefore, using Icelandic classical scrapie as a model prion disease we will focus in this basic research project on the processes of prion strain evolution.
Methodology:
The isolation of Icelandic classical scrapie, limited to one sheep breed and originating from one scrapie infected ram about 150 years ago, together with its well documented history and extended archive, creates unique conditions to study evolution and persistence of prion disease over time. To address our aims four fully interactive work-packages were designed (see project overview):
Host genetics: the extent of prion protein gene (PRNP) variability in Icelandic sheep will be determined and the effect of specific polymorphisms on susceptibility / resistance to classical scrapie will be predicted
Prion Strain evolution: the Icelandic prion strain diversity and the zoonotic potential of Icelandic classical scrapie strains will be analyzed in vitro and in vivo over time to model prion strain evolution
Environmental factors: this work-package includes an analysis how and where classical scrapie infectivity remains in the environment, how effective decontamination is in the field and simultaneously determine the environmental impact on prion strain evolution.
Epidemiological analysis and development of a flexible economic model: classical scrapie outbreaks will be examined to identify risk factors associated with prolonged exposure to classical scrapie that promote recurrent outbreaks. Additionally, based on the results obtained here and in work-packages described above an economic model for classical scrapie response will be developed.
Results:
This project will advance, for the first time, an understanding of the evolution / selection of prion strains in a natural setting, taking into account genetic resistance to infection, prion dissemination, stability and selection in the environment, as well as effective methods for disease control. Hypotheses about the prion strain evolution can thus be tested and the genetic and environmental factors involved can be precisely defined. Flexible epidemiological and economic models will be developed during the project, which will not only benefit classical scrapie control in Iceland, but could also be used for risk assessment and cost- benefit analysis of classical scrapie outbreaks worldwide. The evolution of prion strains has an inherent zoonotic potential and the expected outcomes can be seen as a blueprint for dealing with outbreaks of a potentially zoonotic disease on an international scale.
Involved INNT scientists:
Dr. Christine Fast (project coordinator)
Prof. Dr. Martin Groschup
Lina Spieß
Involved IfE scientist:
Project Partner:
Dr. John Spiropoulos
Animal & Plant Health Agency (APHA)
Prof. Gesine Lühken
Justus-Liebig University of Giessen Institute of Animal Breeding and Genetics
https://www.uni-giessen.de/
Dr. Fiona Houston
University of Edinburgh, UK
https://www.ed.ac.uk/profile/fiona-houston
Dr. Vincent Beringue
Institut national de recherche pour l'agriculture, l'alimentation et l'environnement (INRAe), Jouy En Josas, France
Dr. Juan Carlos Espinosa
Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Madrid, Spain
Inglés Home (inia.es)
Dr. Romolo Nonno
Istituto Superiore di Sanità Food Safety, Nutrition and Veterinary Public Health, Rome, Italy
Dr. Stefania Thorgeirsdottir
Institute for Experimental Pathology at Keldur, University of Iceland Division of Virology and Molecular Biology, Reykjavik, Iceland
English Keldur | Keldur
