Sunday, February 03, 2013
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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