Science, Vol 310, Issue 5746, 324-326 , 14 October 2005
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
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.
To whom correspondence should be addressed. E-mail: adriano@pathol.unizh.ch