title: Coincident scrapie infection and nephritis lead to urinary prion excretion.
abstract: 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.
authors.affiliation: Institute of Neuropathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
authors.forename: Harald
authors.initials: H
authors.lastname: Seeger
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwalder
authors.forename: Nicolas
authors.initials: N
authors.lastname: Zeller
authors.forename: Jan
authors.initials: J
authors.lastname: Kranich
authors.forename: Petra
authors.initials: P
authors.lastname: Schwarz
authors.forename: Ariana
authors.initials: A
authors.lastname: Gaspert
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Seifert
authors.forename: Gino
authors.initials: G
authors.lastname: Miele
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
mesh_terms: 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*
chemical_list: D018620:PrPSc Proteins