Digestion and transportation of bovine spongiform encephalopathy-derived prion protein in the sheep intestine

Mark P. Dagleish, Scott Hamilton, Lorenzo Gonzalez, Samantha L. Eaton, Philip Steele, Jeanie Finlayson, Silvia Siso, Yvonne Pang, Jill Sales, Francesca Chianini, Martin Jeffrey

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Bovine spongiform encephalopathy (BSE) is acquired orally and the mechanisms involved in the absorption and transportation of infectivity across the gut wall are therefore critical Isolated gut loops were created in lambs massaged to remove intestinal contents (flushed) or left non-flushed inoculated with cattle BSE homogenate and excised at different time-points Gut loops were examined by immunohistochemistry (IHC) for disease-associated prion protein (PrPd), and the contents were analysed by Western blotting (WB) to determine the degradation rate of protease-resistant PrP (PrPres) The contents of scrapie-inoculated gut loops from a previous experiment were analysed by WB, and these in vivo digestion results were compared with those of an in vitro experiment on the same transmissible spongiform encephalopathy homogenates BSE-inoculum-derived PrPd was detected by IHC in the gut lumen between 15 min and 3 5 h It was found in the intestinal lymphatic system from 30 min onwards and was present at the highest frequency at 120 min post-inoculation In vivo degradation of PrPres in the BSE inoculum had a significantly (P=0 006) different pattern compared with scrapie-derived PrPres, with the BSE PrPres degrading more rapidly However, the overall amount of degradation became similar by 120 min post-challenge The results of the in vitro digestion experiments showed a similar pattern, although the magnitude of PrPres degradation was less than in the in vivo environment where absorption could also take place BSE-derived PrPres is less protease resistant than scrape PrP over a short time-course and the disappearance of detectable PrPres from the gut lumen results from both absorption and digestion by intestinal contents

Original languageEnglish
Pages (from-to)3116-3123
Number of pages8
JournalJournal of General Virology
Issue number12
Publication statusPublished - Dec 2010

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