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Mucosal transmission and pathogenesis of chronic wasting disease in ferrets

Posted Feb 03 2013 11:37am
Mucosal transmission and pathogenesis of chronic wasting disease in ferrets





Matthew R. Perrott1, Christina J. Sigurdson2, Gary L. Mason3 and Edward A. Hoover3 + Author Affiliations



1Pathobiology, Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand 2Department of Pathology, School of Medicine University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA 3Prion Research Center, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins CO 80523, USA Correspondence Edward A. Hoover edward.hoover@colostate.edu Received 15 July 2012. Accepted 22 October 2012.




Abstract



Chronic wasting disease (CWD) of cervids is almost certainly transmitted by mucosal contact with the causative prion, whether by direct (animal-to-animal) or indirect (environmental) means. Yet the sites and mechanisms of prion entry remain to be further understood. This study sought to extend this understanding by demonstrating that ferrets exposed to CWD via several mucosal routes developed infection, CWD prion protein (PrPCWD) amplification in lymphoid tissues, neural invasion and florid transmissible spongiform encephalopathy lesions resembling those in native cervid hosts. The ferrets developed extensive PrPCWD accumulation in the nervous system, retina and olfactory epithelium, with lesser deposition in tongue, muscle, salivary gland and the vomeronasal organ. PrPCWD accumulation in mucosal sites, including upper respiratory tract epithelium, olfactory epithelium and intestinal Peyer’s patches, make the shedding of prions by infected ferrets plausible. It was also observed that regionally targeted exposure of the nasopharyngeal mucosa resulted in an increased attack rate when compared with oral exposure. The latter finding suggests that nasal exposure enhances permissiveness to CWD infection. The ferret model has further potential for investigation of portals for initiation of CWD infection.










Table S1. Distribution of PrPCWD in ferrets with CWD following atraumatic exposure of mucosal surfaces

The distribution of PrPCWD (by WB and IHC) in the brain of individual ferrets was scored to assess the route of prion entry following i.g. or n.ph. exposure.
−, Absent; +, mild; ++, moderate; +++, extensive. WB scoring was semi-quantitative and was evaluated by comparison with a standard positive control. NT, Not
tested – the entire brain of ferrets 517 and 537 was used to confirm lesion symmetry by IHC.
Brain region I.g. exposure N.ph. exposure
No. 521 No. 547 No. 517 No. 532 No. 537 No. 540
WB IHC WB IHC WB IHC WB IHC WB IHC WB IHC
Brain region
Brainstem +++ ++ + + NT ++ ++ + +++ + ++ +
Cerebellar peduncle +++ ++ + ++ NT + + + NT + ++ +
Ventral midbrain pons +++ NT + + NT + + + NT + ++ +
Dorsal midbrain colliculus +++ NT + + NT + + + NT + ++ +
Hippocampus + + − + NT + − + NT + − +
Occipital cortex + + − + NT + − + NT − − −
Parietal cortex + + + + NT ++ − + NT + − +
Thalamus/hypothalamus ++ NT − − NT ++ + + NT ++ + ++
Olfactory bulb + ++ + + NT ++ +++ + NT ++ + ++
Peripheral tissues*
Olfactory epithelium Pos + + Pos + Pos + Pos ++ ++ Pos ++ Pos +++
Mesenteric node (ROM) Pos Pos + (++)† Pos Pos + (++)† Pos Pos+ Pos Pos ++ Pos Pos Pos Pos +
Retropharyngeal node Pos Pos Pos Pos ++ Pos Pos Pos Pos Pos Pos Pos Pos ++
Peyer’s patches (MP) Pos + Pos + (+)‡ Pos Pos − (+)‡ Pos Pos − (+)‡ Pos + Pos + (−)‡ Pos +(+)‡ Pos Pos Pos −
Spleen Pos Pos ++ Pos Pos + Pos Pos + Pos Pos + Pos Pos Pos Pos+
Tongue NT Pos + NT Pos NT Pos + NT Pos NT Pos + NT Pos +
Salivary/lacrimal glands Pos Pos + Pos Pos + Pos Pos + Pos Pos+ Pos Pos+ Pos Pos ++
Peripheral nervous system Pos Pos + Pos Pos + Pos Pos + Pos Pos + Pos Pos Pos Pos ++
Pancreas/adrenal Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos +
*The broad peripheral distribution of PrPCWD in ferrets inoculated by the oral route and positive (Pos) at this location is shown, whereas peripheral distribution of PrPCWD in i.g.- and
n.ph.-inoculated ferrets is scored. No comparative accumulation is implied as a higher challenge dose was used for the orally inoculated passage 4 ferrets, included here.
†+, Lymph nodes at the root of the mesentery (ROM) were positive for PrPCWD.
‡+, Ganglia of the myenteric plexus (MP) were positive for PrPCWD.


M. R. Perrott, C. J. Sigurdson, G. L. Mason & E. A. Hoover (2013). Mucosal transmission and pathogenesis of chronic wasting disease in ferrets. J Gen Virol 94,

432–442.












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