Abstract
Prions have been documented in extra-neuronal and extra-lymphatic tissues of humans and various ruminants affected by Transmissible Spongiform Encephalopathy (TSE). The presence of prion infectivity detected in cervid and ovine blood tempted us to reason that kidney, the organ filtrating blood derived proteins, may accumulate disease associated PrPSc. We collected and screened kidneys of experimentally, naturally scrapie-affected and control sheep for renal deposition of PrPSc from distinct, geographically separated flocks. By performing Western blot, PET blot analysis and immunohistochemistry we found intraepithelial (cortex, medulla and papilla) and occasional interstitial (papilla) deposition of PrPSc in kidneys of scrapie-affected sheep. Interestingly, glomerula lacked detectable signals indicative of PrPSc. PrPSc was also detected in kidneys of subclinical sheep, but to significantly lower degree. Depending on the stage of the disease the incidence of PrPSc in kidney varied from approximately 27% (subclinical) to 73.6% (clinical) in naturally scrapie-affected sheep. Kidneys from flocks without scrapie outbreak were devoid of PrPSc. Here we demonstrate unexpectedly frequent deposition of high levels of PrPSc in ovine kidneys of various flocks. Renal deposition of PrPSc is likely to be a pre-requisite enabling prionuria, a possible co-factor of horizontal prion-transmission in sheep.
Highlights
Scrapie, a fatal, transmissible spongiform encephalopathy (TSE) of sheep and goat caused by prions, has been intensively studied for more than a century [1]
It is broadly accepted that scrapie is caused by prions, as are bovine spongiform encephalopathy (BSE), Creutzfeldt-Jakob disease (CJD) of humans, including those of sporadic, familial, iatrogenic and variant etiology, chronic wasting disease (CWD) of deer, elk, and moose, and a variety of rarer diseases of several other animal species
All 79 kidney homogenates derived from control Sarda sheep (49 from scrapie affected sheep and 30 from scrapie-free sheep) were negative for PrPSc as analyzed by NaPTA precipitation and conventional Western blot analysis
Summary
A fatal, transmissible spongiform encephalopathy (TSE) of sheep and goat caused by prions, has been intensively studied for more than a century [1]. It is broadly accepted that scrapie is caused by prions, as are bovine spongiform encephalopathy (BSE), Creutzfeldt-Jakob disease (CJD) of humans, including those of sporadic, familial, iatrogenic and variant etiology, chronic wasting disease (CWD) of deer, elk, and moose, and a variety of rarer diseases of several other animal species. PrPSc and/or prion infectivity were demonstrated to accumulate at extraneural and extralymphatic sites, including skeletal muscle, mammary gland, placenta and salivary gland in sheep [7,8,9,10] as well as skeletal muscle [11,12,13,14] and blood in man [15,16] and mice [17] or in saliva [10] and skeletal muscles of deer [18]. Extraneural deposition of PrPSc appears to become prominent in Creutzfeldt-Jakob disease when
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