NR AXZU
AU Zuber,C.; Kolodziejczak,D.; Nikles,D.; Beck,J.; Brenig,B.; Weiss,S.
TI Role of Human Enterocytes and the 37kDa/67kDa Laminin Receptor LRP/LR on the Development of Zoonotic Prion Diseases
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Epidemiology, Risk Assessment and Transmission P04.78
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
TSEs show a species-specific barrier depending on the kind of the incoming prion strain as well as the kind of target organism to be infected. The species barrier results either in altered disease incubation/survival times or even insusceptibility to specific prion strains.
Recently, we found, that BSE-derived prions bound to and became internalized by human enterocytes, the major cell population of the intestinal epithelium, via the 37 kDa/67 kDa laminin receptor LRP/LR (1), acting as a receptor for the cellular prion protein PrPc (2) and infectious PrPsc (3). In contrast, mouse adapted scrapie prions failed to bind to human enterocytes (1), which can be explained by a possible failure
of this prion strain to bind to human LRP/LR on the cell surface. We investigate the species-specific entry barrier in the enterocyte cell system addressing the question whether different animal prion strains such as scrapie in sheep and chronic wasting disease (CWD) in cervids might have the potential to cause a zoonotic disease. The role of LRP/LR in the binding and internalization processes is investigated by the use of anti-LRP specific antibodies such as W3 (4, 5) and scFv S18 (6), as well as polysulfated glycanes targeting LRP/LR (3). Moreover, we show cross-species binding and internalization studies on human and animal enterocytes such as FBJ (bovine), DWM-R (cervids) and IPEC-J2 (procine) with human and animal prions. With this in
vitro cell system we mimic one of the first steps of prions entering the organism. The intestine might represent the crucial barrier for prions deciding upon the development of a zoonotic prion disease, which might be caused by sheep scrapie and CWD.
(1) Morel et al. (2005) Am. J. Path. 167, 1033-1042. (2) Gauczynski et al. (2001) EMBO J. 20, 5863-5875. (3) Gauczynski et al., (2006) J. Infect. Dis.. 194, 702-709; (4) Leucht et al. (2003) EMBO rep 4, 290-295; (5) Zuber et al., Mol. Ther. Revised; (6) Zuber et al., Mol Immunol., in press.
AD C. Zuber, D. Kolodziejczak, D. Nikles, S. Weiss, Gene Center, Institute of Biochemistry, Germany; J. Beck, B. Brenig, University of Göttingen, Veterinary Institute, Germany
SP englisch
PO Schottland