Faecal shedding, alimentary clearance and intestinal spread of prions in hamsters fed with scrapieDominique Krüger1, Achim Thomzig1, Gudrun Lenz1, Kristin Kampf1, Patricia McBride2 and Michael Beekes1
1 Robert Koch-Institute, P24-Transmissible Spongiform Encephalopathies, Nordufer 20, D-13353 Berlin, Germany
2 Institute for Animal Health, Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, United Kingdom
Received 1 November 2007; accepted 29 September 2008; published online 3 October 2008
Abstract - Shedding of prions via faeces may be involved in the transmission of contagious prion diseases. Here, we fed hamsters 10mg of 263K scrapie brain homogenate and examined the faecal excretion of disease-associated prion protein (PrP) during the course of infection. The intestinal fate of ingested PrP was further investigated by monitoring the deposition of the protein in components of the gut wall using immunohistochemistry and paraffin-embedded tissue (PET) blotting. Western blotting of faecal extracts showed shedding of PrP in the excrement at 24–72 h post infection (hpi), but not at 0–24 hpi or at later preclinical or clinical time points. About 5% of the ingested PrP were excreted via the faeces. However, the bulk of PrP was cleared from the alimentary canal, most probably by degradation, while an indiscernible proportion of the inoculum triggered intestinal infection. Components of the gut-associated lymphoid tissue (GALT) and the enteric nervous system (ENS) showed progressing accumulation of PrP from 30 days post infection (dpi) and 60 dpi, respectively. At the clinical stage of disease, substantial deposits of PrP were found in the GALT in close vicinity to the intestinal lumen. Despite an apparent possibility of shedding from Peyer's patches that may involve the follicle-associated epithelium (FAE), only small amounts of PrP were detected in faeces from clinically infected animals by serial protein misfolding cyclic amplification (sPMCA). Although excrement may thus provide a vehicle for the release of endogenously formed PrP, intestinal clearance mechanisms seem to partially counteract such a mode of prion dissemination.
Key words: prion / oral infection / Peyer's patches / enteric nervous system / faeces
Corresponding author: BeekesM@rki.de
© INRA, EDP Sciences 2008