Susceptibility of Domestic Cats to Chronic Wasting Disease

Mathiason, Candace K.; Nalls, Amy V.; Seelig, Davis; Kraft, Susan L.; Carnes, K. D.; Anderson, Kelly; Hayes-Klug, Jeanette; Hoover, Edward A.

doi:10.1128/jvi.02592-12

Cited by 59 publications

(50 citation statements)

References 65 publications

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“…It is to be noted that in a previous study, however, we found the CER assay resulted in a similar pattern of PrP res formation as that of PMCA 15 . The results presented here also indicate that the CER assay correctly predicts the species barriers for transmission of various TSEs to laboratory mice (Figure 3) and suggest that bobcats may have susceptibility to CWD (Figure 4), in agreement with reports that domestic cats (Felis catus) can acquire prion disease after experimental CWD challenge 26,27 . Studies using the CER assay could compliment PrP sequencing efforts to understand wildlife susceptibility to CWD 28 .…”

Section: Discussionsupporting

confidence: 76%

Assessing Transmissible Spongiform Encephalopathy Species Barriers with an <em>In Vitro</em> Prion Protein Conversion Assay

Johnson

Carlson

Morawski

et al. 2015

JoVE

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Studies to understanding interspecies transmission of transmissible spongiform encephalopathies (TSEs, prion diseases) are challenging in that they typically rely upon lengthy and costly in vivo animal challenge studies. A number of in vitro assays have been developed to aid in measuring prion species barriers, thereby reducing animal use and providing quicker results than animal bioassays. Here, we present the protocol for a rapid in vitro prion conversion assay called the conversion efficiency ratio (CER) assay. In this assay cellular prion protein (PrP C ) from an uninfected host brain is denatured at both pH 7.4 and 3.5 to produce two substrates. When the pH 7.4 substrate is incubated with TSE agent, the amount of PrP C that converts to a proteinase K (PK)-resistant state is modulated by the original host's species barrier to the TSE agent. In contrast, PrP C in the pH 3.5 substrate is misfolded by any TSE agent. By comparing the amount of PK-resistant prion protein in the two substrates, an assessment of the host's species barrier can be made. We show that the CER assay correctly predicts known prion species barriers of laboratory mice and, as an example, show some preliminary results suggesting that bobcats (Lynx rufus) may be susceptible to whitetailed deer (Odocoileus virginianus) chronic wasting disease agent. Video LinkThe video component of this article can be found at

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Section: Discussionsupporting

confidence: 76%

Assessing Transmissible Spongiform Encephalopathy Species Barriers with an <em>In Vitro</em> Prion Protein Conversion Assay

Johnson

Carlson

Morawski

et al. 2015

JoVE

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“…37 These results of these studies (1) provide morphologic evidence of serial passage–associated prion adaptation, (2) illustrate a unique phenotype of cellular and subcellular brain PrP D accumulation, and (3) generate a novel Fel CWD neuropathologic profile that could be used to discriminate Fel CWD from FSE should natural prion infection be detected in a domestic felid.…”

Section: Discussionmentioning

confidence: 92%

Lesion Profiling and Subcellular Prion Localization of Cervid Chronic Wasting Disease in Domestic Cats

et al. 2014

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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.

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“…Despite its rampant spread among cervids, natural cross-species transmission of CWD appears to be highly restricted. However, experimentally, transmission has been demonstrated in squirrel monkeys (87), domestic cats (88), voles, golden hamsters, minks, ferrets, goats, and cattle (reviewed in 50). However, macaques have shown resistance to CWD infection (113), implying that CWD is not likely to be readily transmissible to humans.…”

Section: Transmissibility Of Prionsmentioning

confidence: 99%

Prions and the Potential Transmissibility of Protein Misfolding Diseases

Kraus

Groveman

Caughey

2013

Annu. Rev. Microbiol.

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Prions, or infectious proteins, represent a major frontier in the study of infectious agents. The prions responsible for mammalian transmissible spongiform encephalopathies (TSEs) are due primarily to infectious self-propagation of misfolded prion proteins. TSE prion structures remain ill-defined, other than being highly structured, self-propagating, and often fibrillar protein multimers with the capacity to seed, or template, the conversion of their normal monomeric precursors into a pathogenic form. Purified TSE prions usually take the form of amyloid fibrils, which are self-seeding ultrastructures common to many serious protein misfolding diseases such as Alzheimer’s, Parkinson’s, Huntington’s and Lou Gehrig’s (amytrophic lateral sclerosis). Indeed, recent reports have now provided evidence of prion-like propagation of several misfolded proteins from cell to cell, if not from tissue to tissue or individual to individual. These findings raise concerns that various protein misfolding diseases might have spreading, prion-like etiologies that contribute to pathogenesis or prevalence.

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Susceptibility of Domestic Cats to Chronic Wasting Disease

Cited by 59 publications

References 65 publications

Assessing Transmissible Spongiform Encephalopathy Species Barriers with an <em>In Vitro</em> Prion Protein Conversion Assay

Assessing Transmissible Spongiform Encephalopathy Species Barriers with an <em>In Vitro</em> Prion Protein Conversion Assay

Lesion Profiling and Subcellular Prion Localization of Cervid Chronic Wasting Disease in Domestic Cats

Prions and the Potential Transmissibility of Protein Misfolding Diseases

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