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Peggy Rigou 1 Sylvie Noinville 1 Yann Quenet 1 Human Rezaei 1 Siobhan Staunton 2 Herve Quiquampoix 2 Pierre Sarradin 3 Celine Barc 3 Frédéric Lantier 3 Patricia Berthon 3 Serge Bernard 3 Jeanne Grosclaude 1
Abstract : Better control of domestic animal prion diseases is currently achieved through sanitary provisions and genetic selection for resistant sheep.The persistence of an environmental reservoir for infectivity would counteract this progress, particularly in the wild. Abiotic mechanisms of prion retention and dissemination in soil were first investigated by studying interaction between a pure clay (Montmorillonite or Mt) and a model oligomeric prion protein mimicking the pathological isoform; these physico-chemical approaches (mainly FTIR-spectrometry, RMN studies, biochemical and immunochemical depletion studies) allowed to reason infectivity studies with infected brain homogenates adsorbed on Mt. Clays are known for displaying a high adsorption capacity for proteins, due to their negative permanent charge and their high specific area (800 square metres for one gramme of sodic montmorillonite). Adsorption of PrPrec to Mt ranged from 1g protein / g Mt at pH 3-5 to more than 2 g protein / g Mt at neutral/alcaline pH. The mechanism relied mainly on the two-domain structure of the prion protein, allowing a strong interaction of the positively charged N-terminal domain and a hydrophobic-like interaction of the full-length protein with the Mt surface (Revault et al., 2005, BBA, 1724,367). Protein desorption from Mt could not be achieved by saline, detergent or chaotropic reagents supporting irreversibility of adsorption in environmental conditions. Moreover when competing with other biological material such as serum proteins, PrPrec was selectively adsorbed by Mt. So Mt behaves as a strong concentrating agent for prion protein (Rigou et al., 2006, Environ.Sci.Technol, 40,1479). In natural conditions Mt might constitute "infectivity hot points" from trace amounts of infected biological material recurrently deposited on soil like in whelping areas. Mt efficiency in capturing infectivity from infected organs was checked in bioassays on transgenic mice. Infectivity experiments emphasized the infectious capacity of contaminated Mt devoid of any biological debris after one night contact with infected brain homogenates. Fate of Mt-adsorbed labelled PrP in brain after inoculation or in gut after ingestion was followed by dynamic imaging techniques. Implications of these results for environmental control of prion diseases will be discussed taking into account recent publications from other research groups.