Excretion of transmissible spongiform encephalopathy infectivity in urine

Abstract

The route of transmission of most naturally acquired transmissible spongiform encephalopathy (TSE) infections remains speculative. To investigate urine as a potential source of TSE exposure, we used a sensitive method for detection and quantitation of TSE infectivity. Pooled urine collected from 22 hamsters showing clinical signs of 263K scrapie contained 3.8 +/- 0.9 infectious doses/mL of infectivity. Titration of homogenates of kidneys and urinary bladders from the same animals gave concentrations 20,000-fold greater. Histologic and immunohistochemical examination of these same tissues showed no indications of inflammatory or other pathologic changes except for occasional deposits of disease-associated prion protein in kidneys. Although the source of TSE infectivity in urine remains unresolved, these results establish that TSE infectivity is excreted in urine and may thereby play a role in the horizontal transmission of natural TSEs. The results also indicate potential risk for TSE transmission from human urine-derived hormones and other medicines.

Figure 1

Distribution of incubation times of hamsters infected by injected urine. Each dot represents 1 animal with clinical scrapie that was euthanized at the corresponding day postinoculation. The 22 additional animals that died during the incubation period and the 252 animals that survived to the end of the experiment (559 days) showed no clinical or immunochemical evidence of scrapie and were scored as scrapie negative.

Figure 2

Immunostaining for prion protein (PrP) in control and scrapie-infected hamsters. Deposition of disease-associated PrP is lacking in the brain (A), spleen (B), and kidneys (C,D) of control hamsters. Fine synaptic and plaque-like PrP immunoreactivity in the frontal cortex (E), granular immunoreactivity in the germinal center of spleen (F) and in the collecting tubules of kidneys (G,H) in a representative scrapie-infected animal. Original magnification ×200 for panels A, B, D, E, F, and H and ×40 for panels C and G.