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Science 14 October 2005:
Vol. 310. no. 5746, pp. 324 - 326
DOI: 10.1126/science.1118829
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Reports

Coincident Scrapie Infection and Nephritis Lead to Urinary Prion Excretion

Harald Seeger,1* Mathias Heikenwalder,1* Nicolas Zeller,1 Jan Kranich,1 Petra Schwarz,1 Ariana Gaspert,2 Burkhardt Seifert,3 Gino Miele,1 Adriano Aguzzi1{dagger}

Prion infectivity is typically restricted to the central nervous and lymphatic systems of infected hosts, but chronic inflammation can expand the distribution of prions. We tested whether chronic inflammatory kidney disorders would trigger excretion of prion infectivity into urine. Urinary proteins from scrapie-infected mice with lymphocytic nephritis induced scrapie upon inoculation into noninfected indicator mice. Prionuria was found in presymptomatic scrapie-infected and in sick mice, whereas neither prionuria nor urinary PrPSc was detectable in prion-infected wild-type or PrPC-overexpressing mice, or in nephritic mice inoculated with noninfectious brain. Thus, urine may provide a vector for horizontal prion transmission, and inflammation of excretory organs may influence prion spread.

1 Institute of Neuropathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
2 Institute of Clinical Pathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
3 Institute of Biostatistics, University of Zürich, Sumatrastrasse 30, CH-8006 Zürich, Switzerland.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: adriano{at}pathol.unizh.ch

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