title: Primary transmission of chronic wasting disease versus scrapie prions from small ruminants to transgenic mice expressing ovine or cervid prion protein.
abstract: Development of mice expressing either ovine (Tg338) or cervid (TgElk) prion protein (PrP) have aided in characterization of scrapie and chronic wasting disease (CWD), respectively. Experimental inoculation of sheep with CWD prions has demonstrated the potential for interspecies transmission but, infection with CWD versus classical scrapie prions may be difficult to differentiate using validated diagnostic platforms. In this study, mouse bioassay in Tg338 and TgElk was utilized to evaluate transmission of CWD versus scrapie prions from small ruminants. Mice (≥5 per homogenate) were inoculated with brain homogenates from clinically affected sheep or goats with naturally acquired classical scrapie, white-tailed deer with naturally acquired CWD (WTD-CWD) or sheep with experimentally acquired CWD derived from elk (sheep-passaged-CWD). Survival time (time to clinical disease) and attack rates (brain accumulation of protease resistant PrP, PrPres) were determined. Inoculation with classical scrapie prions resulted in clinical disease and 100 % attack rates in Tg338, but no clinical disease at endpoint (>300 days post-inoculation, p.i.) and low attack rates (6.8 %) in TgElk. Inoculation with WTD-CWD prions yielded no clinical disease or brain PrPres accumulation in Tg338 at endpoint (>500 days p.i.), but rapid onset of clinical disease (~121 days p.i.) and 100 % attack rate in TgElk. Sheep-passaged-CWD resulted in transmission to both mouse lines with 100 % attack rates at endpoint in Tg338 and an attack rate of ~73 % in TgElk with some culled due to clinical disease. These primary transmission observations demonstrate the potential of bioassay in Tg338 and TgElk to help differentiate possible infection with CWD versus classical scrapie prions in sheep and goats.
authors.affiliation: Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Madsen-Bouterse
authors.affiliation: Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7040, USA.|Animal Disease Research Unit, Agricultural Research Service, US Department of Agriculture, Pullman, WA 99164-6630, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Schneider
authors.affiliation: Animal Disease Research Unit, Agricultural Research Service, US Department of Agriculture, Pullman, WA 99164-6630, USA.
authors.forename: Dongyue
authors.initials: D
authors.lastname: Zhuang
authors.affiliation: Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7040, USA.
authors.forename: Rohana P
authors.initials: RP
authors.lastname: Dassanayake
authors.affiliation: National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection, Agency, Ottawa Laboratory-Fallowfield, Ottawa, Ontario, Canada.
authors.forename: Aru
authors.initials: A
authors.lastname: Balachandran
authors.affiliation: National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection, Agency, Ottawa Laboratory-Fallowfield, Ottawa, Ontario, Canada.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mitchell
authors.affiliation: Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7040, USA.|Animal Disease Research Unit, Agricultural Research Service, US Department of Agriculture, Pullman, WA 99164-6630, USA.
authors.forename: Katherine I
authors.initials: KI
authors.lastname: O'Rourke
mesh_terms: D000818:Animals; D003670:Deer; D004195:Disease Models, Animal; D006041:Goats; D051379:Mice; D008822:Mice, Transgenic; D011328:Prions / Q000235:genetics*; D012608:Scrapie / Q000635:transmission*; D012756:Sheep; D016019:Survival Analysis; D034081:Wasting Disease, Chronic / Q000635:transmission*
chemical_list: D011328:Prions