Urine from Scrapie-Infected Hamsters Comprises Low Levels of Prion Infectivity

Abstract

The question of whether prion diseases can be transmitted by body fluids has important epidemiological, environmental and economical implications. In this work, we set to investigate whether urine collected from scrapie-infected hamsters can transmit fatal or subclinical infectivity to normal hamsters. After prolonged incubation times ranging from 300 to 700 days, a small number of animals inoculated with scrapie urine succumbed to scrapie disease, and several asymptomatic hamsters presented low levels of PrP^Sc in their brains. In addition, most of the asymptomatic hamsters inoculated with scrapie urine, as opposed to those inoculated with normal urine, presented extensive gliosis as well as protease-resistant light chain IgG in their urine, a molecule shown by us and others to be a surrogate marker for prion infection. Our results suggest that urine from scrapie-infected hamsters can transmit a widespread subclinical disease that in some cases develops into fatal scrapie.

Prion Disease Detection, PMCA Kinetics, and IgG in Urine from Sheep Naturally/Experimentally Infected with Scrapie and Deer with Preclinical/Clinical Chronic Wasting Disease

“…Similarly, reports on the detection of PrP Sc in urine were initially met with controversy (20,29,30) but have become more, but not universally, convincing with the advent of PMCA FIG. 4.…”

“…Attempts to demonstrate the TSE infectious agent in urine through transmission studies have been unrewarding as well as inconsistently and variably successful (2,12,14,15,20,28). Similarly, reports on the detection of PrP Sc in urine were initially met with controversy (20,29,30) but have become more, but not universally, convincing with the advent of PMCA FIG.…”

“…Some of these have not been successful (2,12), presumably due to the species barrier between the host source and test animals inoculated. More recent studies with urine from rodents and cervids have been more successful, albeit still limited and variable (14,15,17,20,28,30). Two of these have reported infectivity in urine (28) and infectivity with PrP Sc in kidneys of mice with simultaneous scrapie infection and nephritis but not in those with scrapie infection alone (17).…”

“…However, subsequent studies failed to detect PrP Sc in urine from prion disease-affected individuals and demonstrated that the false-positive results arose from the cross-reaction of anti-mouse IgG with either contaminating bacterial proteins (11) or urinary IgG fragments (29). PrP Sc has been identified by serial protein misfolding cyclic amplification (PMCA) in the urine of scrapie-infected sheep, hamsters, and mice and infrequently in both chronic wasting disease (CWD)-infected deer and transgenic mice (2,13,14,20,24). Further, it has been shown that a major protease-resistant protein in urine from prion disease-affected humans and animals is light chain IgG (15,29).…”

Excretion of Transmissible Spongiform Encephalopathy Infectivity in Urine

“…More recent attempts in which urine from infected hamsters was injected back into hamsters have produced variable results (9,10). Two other studies have reported infectivity in urine (11) and infectivity with disease-specifi c prion protein (PrP d ) in kidneys of mice with simultaneous scrapie and nephritis but not in those with scrapie alone (12).…”