Chronic Wasting Disease (CWD) Susceptibility of Several North American Rodents That Are Sympatric with Cervid CWD Epidemics

Heisey, Dennis M.; Mickelsen, Natalie A.; Schneider, Jay R.; Johnson, Christopher; Johnson, Chad; Langenberg, Julia A.; Bochsler, Philip N.; Keane, Delwyn P.; Barr, Daniel J.

doi:10.1128/jvi.00560-09

Cited by 60 publications

(53 citation statements)

References 28 publications

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“…Heisey et al (14) previously reported a median survival time of 270 dpi for M. pennsylvanicus i.c. challenged with CWD-positive Wisconsin white-tailed deer brain homogenate.…”

Section: Discussionmentioning

confidence: 99%

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Alteration of the Chronic Wasting Disease Species Barrier byIn VitroPrion Amplification

Kurt

Seelig

Schneider

et al. 2011

J Virol

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Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of cervids now detected in 19 states of the United States, three Canadian provinces, and South Korea. Whether noncervid species can be infected by CWD and thereby serve as reservoirs for the infection is not known. To investigate this issue, we previously used serial protein misfolding cyclic amplification (sPMCA) to demonstrate that CWD prions can amplify in brain homogenates from several species sympatric with cervids, including prairie voles (Microtus ochrogaster) and field mice (Peromyscus spp.). Here, we show that prairie voles are susceptible to mule deer CWD prions in vivo and that sPMCA amplification of CWD prions in vole brain enhances the infectivity of CWD for this species. Prairie voles inoculated with sPMCA products developed clinical signs of TSE disease approximately 300 days prior to, and more consistently than, those inoculated with CWD prions from deer brain. Moreover, the deposition patterns and biochemical properties of protease-resistant form of PrP (PrP RES ) in the brains of affected voles differed from those in cervidized transgenic (CerPrP) mice infected with CWD. In addition, voles inoculated orally with sPMCA products developed clinical signs of TSE and were positive for PrP RES deposition, whereas those inoculated orally with deer-origin CWD prions did not. These results demonstrate that transspecies sPMCA of CWD prions can enhance the infectivity and adapt the host range of CWD prions and thereby may be useful to assess determinants of prion species barriers.Chronic wasting disease (CWD) is a fatal transmissible spongiform encephalopathy (TSE) of cervids, including deer, elk, and moose. CWD is the only TSE found in free-ranging wildlife; its spread in nature may reflect the dissemination of prions from saliva and excreta of infected cervids (10,20,22,28,36) and/or the persistence of infectious prions in the environment (15,23,30). While the known natural host range for CWD is limited to cervids, recent studies have expanded the number of noncervid species (ferrets, mink, hamsters, cattle, sheep, Peromyscus spp. mice, and voles) that can be infected experimentally (3, 11-14, 26, 32). It is not known whether noncervid species may contribute to the spread of CWD as reservoirs or vectors; however, interspecies transmission of prion diseases (e.g., from deer to noncervids) is less efficient than intraspecies transmission, a phenomenon commonly referred to as a species barrier. Species barriers may be mediated by differences in cellular PrP (PrP C ) sequence (5, 13, 16), inoculum titer, route of inoculation, and other still unknown factors (4,13,16,24,25).We recently demonstrated (18) that PrP C from several noncervid species, including prairie voles (Microtus ochrogaster) and prairie deer mice (Peromyscus maniculatus bairdii), can be converted to the protease-resistant form of PrP (PrP RES ) in vitro by serial protein misfolding cyclic amplification (sPMCA). Heisey et al. (14) have since shown that other vol...

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“…Heisey et al (14) previously reported a median survival time of 270 dpi for M. pennsylvanicus i.c. challenged with CWD-positive Wisconsin white-tailed deer brain homogenate.…”

Section: Discussionmentioning

confidence: 99%

“…Heisey et al (14) have since shown that other vole and Peromyscus species are indeed susceptible to intracerebral (i.c.) inoculation with CWD.…”

mentioning

confidence: 99%

Alteration of the Chronic Wasting Disease Species Barrier byIn VitroPrion Amplification

Kurt

Seelig

Schneider

et al. 2011

J Virol

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“…[22][23][24] However, intracerebral CWD inoculation caused prion infection in voles, hamsters, ferrets, sheep, cats, mink, and cattle, with variable attack rates. [25][26][27][28][29][30][31][32][33] Wild type mice and raccoons resisted CWD prion infection (Table 1). 16,34,35 An extensive study of CWD susceptibility in transgenic mice expressing ovine and bovine PrP C revealed no mice with prion disease, supporting the strong barrier to CWD infection observed in sheep and cattle.…”

Section: Cross-species Cwd Prion Transmissionmentioning

confidence: 99%

Cross-species transmission of CWD prions

Kurt

Sigurdson

2016

Prion

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“…Rodents have been hypothesized to be potential reservoirs of TSEs (Heisey et al 2010). Therefore, we specifically extended the PRNP and PRND data sets for diverse rodent species.…”

Section: Discussionmentioning

confidence: 99%

Negative Purifying Selection Drives Prion and Doppel Protein Evolution

et al. 2014

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The prion protein (PrP) when misfolded into the pathogenic conformer PrP Sc is the major causative agent of several lethal transmissible spongiform encephalopathies in mammals. Studies of evolutionary pressure on the corresponding gene using different datasets have yielded conflicting results. In addition, putative PrP or PrP interacting partners with strong similarity to PrP such as the doppel protein have not been examined to determine if the same evolutionary mechanisms apply to prion paralogs or if there are coselected sites that might indicate how and where the proteins interact. We examined several taxonomic groups that contain model organisms of prion diseases focusing on primates, bovids, and an expanded dataset of rodents for selection pressure on the prion gene (PRNP) and doppel gene (PRND) individually and for coevolving sites within. Overall, the results clearly indicate that both proteins are under strong selective constraints with relaxed selection on amino acid residues connecting a-helices 1 and 2.

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Chronic Wasting Disease (CWD) Susceptibility of Several North American Rodents That Are Sympatric with Cervid CWD Epidemics

Cited by 60 publications

References 28 publications

Alteration of the Chronic Wasting Disease Species Barrier byIn VitroPrion Amplification

Alteration of the Chronic Wasting Disease Species Barrier byIn VitroPrion Amplification

Cross-species transmission of CWD prions

Negative Purifying Selection Drives Prion and Doppel Protein Evolution

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