Coincident scrapie infection and nephritis lead to urinary prion excretion.
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 PrP(Sc) was detectable in prion-infected wild-type or PrP(C)-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.
Seeger
Harald
H
Institute of Neuropathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
Heikenwalder
Mathias
M
Zeller
Nicolas
N
Kranich
Jan
J
Schwarz
Petra
P
Gaspert
Ariana
A
Seifert
Burkhardt
B
Miele
Gino
G
Aguzzi
Adriano
A
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D009393:Nephritis / Q000150:complications / Q000652:urine*; D018620:PrPSc Proteins / Q000652:urine*; D012608:Scrapie / Q000150:complications / Q000473:pathology / Q000635:transmission / Q000652:urine*
D018620:PrPSc Proteins