Abstract
Chronic wasting disease (CWD) is an efficiently transmitted, fatal, and progressive prion disease of cervids with an as yet to be fully clarified host range. While outbred domestic cats (Felis catus) have recently been shown to be susceptible to experimental CWD infection, the neuropathologic features of the infection are lacking. Such information is vital to provide diagnostic power in the event of natural interspecies transmission and insights into host and strain interactions in interspecies prion infection. Using light microscopy and immunohistochemistry, we detail the topographic pattern of neural spongiosis (the “lesion profile”) and the distribution of misfolded prion protein in the primary and secondary passage of feline CWD (FelCWD). We also evaluated cellular and subcellular associations between misfolded prion protein (PrPD) and central nervous system neurons and glial cell populations. From these studies, we (1) describe the novel neuropathologic profile of FelCWD, which is distinct from either cervid CWD or feline spongiform encephalopathy (FSE), and (2) provide evidence of serial passage-associated interspecies prion adaptation. In addition, we demonstrate through confocal analysis the successful co-localization of PrPD with neurons, astrocytes, microglia, lysosomes, and synaptophysin, which, in part, implicates each of these in the neuropathology of FelCWD. In conclusion, this work illustrates the simultaneous role of both host and strain in the development of a unique FelCWD neuropathologic profile and that such a profile can be used to discriminate between FelCWD and FSE.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 107-119 |
| Number of pages | 13 |
| Journal | Veterinary pathology |
| Volume | 52 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 29 2015 |
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Keywords
- adaptation
- cat
- chronic wasting disease
- feline spongiform encephalopathy
- immunohistochemistry
- interspecies
- prion
- species barrier
- transmissible spongiform encephalopathy
Cite this
Lesion Profiling and Subcellular Prion Localization of Cervid Chronic Wasting Disease in Domestic Cats. / Seelig, Davis; Nalls, A. V.; Flasik, M.; Frank, V.; Eaton, S.; Mathiason, C. K.; Hoover, E. A.
In: Veterinary pathology, Vol. 52, No. 1, 29.01.2015, p. 107-119.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lesion Profiling and Subcellular Prion Localization of Cervid Chronic Wasting Disease in Domestic Cats
AU - Seelig, Davis
AU - Nalls, A. V.
AU - Flasik, M.
AU - Frank, V.
AU - Eaton, S.
AU - Mathiason, C. K.
AU - Hoover, E. A.
PY - 2015/1/29
Y1 - 2015/1/29
N2 - Chronic wasting disease (CWD) is an efficiently transmitted, fatal, and progressive prion disease of cervids with an as yet to be fully clarified host range. While outbred domestic cats (Felis catus) have recently been shown to be susceptible to experimental CWD infection, the neuropathologic features of the infection are lacking. Such information is vital to provide diagnostic power in the event of natural interspecies transmission and insights into host and strain interactions in interspecies prion infection. Using light microscopy and immunohistochemistry, we detail the topographic pattern of neural spongiosis (the “lesion profile”) and the distribution of misfolded prion protein in the primary and secondary passage of feline CWD (FelCWD). We also evaluated cellular and subcellular associations between misfolded prion protein (PrPD) and central nervous system neurons and glial cell populations. From these studies, we (1) describe the novel neuropathologic profile of FelCWD, which is distinct from either cervid CWD or feline spongiform encephalopathy (FSE), and (2) provide evidence of serial passage-associated interspecies prion adaptation. In addition, we demonstrate through confocal analysis the successful co-localization of PrPD with neurons, astrocytes, microglia, lysosomes, and synaptophysin, which, in part, implicates each of these in the neuropathology of FelCWD. In conclusion, this work illustrates the simultaneous role of both host and strain in the development of a unique FelCWD neuropathologic profile and that such a profile can be used to discriminate between FelCWD and FSE.
AB - Chronic wasting disease (CWD) is an efficiently transmitted, fatal, and progressive prion disease of cervids with an as yet to be fully clarified host range. While outbred domestic cats (Felis catus) have recently been shown to be susceptible to experimental CWD infection, the neuropathologic features of the infection are lacking. Such information is vital to provide diagnostic power in the event of natural interspecies transmission and insights into host and strain interactions in interspecies prion infection. Using light microscopy and immunohistochemistry, we detail the topographic pattern of neural spongiosis (the “lesion profile”) and the distribution of misfolded prion protein in the primary and secondary passage of feline CWD (FelCWD). We also evaluated cellular and subcellular associations between misfolded prion protein (PrPD) and central nervous system neurons and glial cell populations. From these studies, we (1) describe the novel neuropathologic profile of FelCWD, which is distinct from either cervid CWD or feline spongiform encephalopathy (FSE), and (2) provide evidence of serial passage-associated interspecies prion adaptation. In addition, we demonstrate through confocal analysis the successful co-localization of PrPD with neurons, astrocytes, microglia, lysosomes, and synaptophysin, which, in part, implicates each of these in the neuropathology of FelCWD. In conclusion, this work illustrates the simultaneous role of both host and strain in the development of a unique FelCWD neuropathologic profile and that such a profile can be used to discriminate between FelCWD and FSE.
KW - adaptation
KW - cat
KW - chronic wasting disease
KW - feline spongiform encephalopathy
KW - immunohistochemistry
KW - interspecies
KW - prion
KW - species barrier
KW - transmissible spongiform encephalopathy
UR - http://www.scopus.com/inward/record.url?scp=84919976415&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84919976415&partnerID=8YFLogxK
U2 - 10.1177/0300985814524798
DO - 10.1177/0300985814524798
M3 - Article
C2 - 24577721
AN - SCOPUS:84919976415
VL - 52
SP - 107
EP - 119
JO - Veterinary Pathology
JF - Veterinary Pathology
SN - 0300-9858
IS - 1
ER -