Experimental Chronic Wasting Disease in Wild Type VM Mice

Lee, Yoon-Hee; Sohn, Hyun‐Joo; Kim, Minjeong; Kim, Hyojin; Park, Kyung-Je; Lee, Won Young; Yun, Eun-Im; Tark, Dongseob; Choi, Y.P.; Cho, In‐Soo; Balachandran, Aru

doi:10.1292/jvms.13-0018

Cited by 18 publications

(23 citation statements)

References 14 publications

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“…Moreover, this appears to be how outbreaks of the disease occurred in elk in the Republic of Korea in 2001, 2004, and 2005—as a result of the country’s importation of subclinically infected animals (Sohn et al 2002; Kim et al 2005). In 2010, additional CWD cases were observed in red deer ( Cervus elaphus ), sika deer ( Cervus nippon ), and crossbred sika and red deer (Lee et al 2013). …”

Section: Epidemiology and Host Rangementioning

confidence: 99%

Molecular Mechanisms of Chronic Wasting Disease Prion Propagation

Moreno

Telling

2017

Cold Spring Harb Perspect Med

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Prion disease epidemics, which have been unpredictable recurrences, are of significant concern for animal and human health. Examples include kuru, once the leading cause of death among the Fore people in Papua New Guinea and caused by mortuary feasting; bovine spongiform encephalopathy (BSE) and its subsequent transmission to humans in the form of variant Creutzfeldt-Jakob disease (vCJD); and repeated examples of large-scale prion disease epidemics in animals caused by contaminated vaccines. The etiology of chronic wasting disease (CWD), a relatively new and burgeoning prion epidemic in deer, elk, and moose (members of the cervid family), is more enigmatic. The disease was first described in captive and later in wild mule deer and subsequently in free-ranging as well as captive Rocky Mountain elk, white-tailed deer, and most recently moose. It is therefore the only recognized prion disorder of both wild and captive animals. In addition to its expanding range of hosts, CWD continues to spread to new geographical areas, including recent cases in Norway. The unparalleled efficiency of the contagious transmission of the disease combined with high densities of deer in certain areas of North America complicates strategies for controlling CWD and raises concerns about its potential spread to new species. Because there is a high prevalence of CWD in deer and elk, which are commonly hunted and consumed by humans, the possibility of zoonotic transmission is particularly concerning. Here we review the current status of naturally occurring CWD and describe advances in our understanding of its molecular pathogenesis, as shown by studies of CWD prions in novel in vivo and in vitro systems.

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Section: Epidemiology and Host Rangementioning

confidence: 99%

Molecular Mechanisms of Chronic Wasting Disease Prion Propagation

Moreno

Telling

2017

Cold Spring Harb Perspect Med

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“…On first passage, all inoculated animals either remain asymptomatic for extended periods (3)(4)(5)(6)(7)(8)(9) or may develop disease after a prolonged asymptomatic phase (8,10,11). In a third alternative, only a subpopulation develops disease, with variable incubation times (8,12,13). However, in all cases, secondary transmission results in shorter, synchronous times to disease in all recipients.…”

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confidence: 99%

Prion replication without host adaptation during interspecies transmissions

Bian

Khaychuk

Angers

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Adaptation of prions to new species is thought to reflect the capacity of the host-encoded cellular form of the prion protein (PrPC) to selectively propagate optimized prion conformations from larger ensembles generated in the species of origin. Here we describe an alternate replicative process, termed nonadaptive prion amplification (NAPA), in which dominant conformers bypass this requirement during particular interspecies transmissions. To model susceptibility of horses to prions, we produced transgenic (Tg) mice expressing cognate PrPC. Although disease transmission to only a subset of infected TgEq indicated a significant barrier to EqPrPCconversion, the resulting horse prions unexpectedly failed to cause disease upon further passage to TgEq. TgD expressing deer PrPCwas similarly refractory to deer prions from diseased TgD infected with mink prions. In both cases, the resulting prions transmitted to mice expressing PrPCfrom the species of prion origin, demonstrating that transmission barrier eradication of the originating prions was ephemeral and adaptation superficial in TgEq and TgD. Horse prions produced in vitro by protein misfolding cyclic amplification of mouse prions using horse PrPCalso failed to infect TgEq but retained tropism for wild-type mice. Concordant patterns of neuropathology and prion deposition in susceptible mice infected with NAPA prions and the corresponding prion of origin confirmed preservation of strain properties. The comparable responses of both prion types to guanidine hydrochloride denaturation indicated this occurs because NAPA precludes selection of novel prion conformations. Our findings provide insights into mechanisms regulating interspecies prion transmission and a framework to reconcile puzzling epidemiological features of certain prion disorders.

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“…hronic wasting disease (CWD) is a burgeoning transmissible spongiform encephalopathy (TSE) epidemic of captive and free-ranging cervids in North America and South Korea (1,2). CWD is the only known TSE of wild animals and appears to be transmitted with unprecedented efficiency.…”

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confidence: 99%

Assessing the Susceptibility of Transgenic Mice Overexpressing Deer Prion Protein to Bovine Spongiform Encephalopathy

Vickery

Lockey

Holder

et al. 2014

J Virol

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cSeveral transgenic mouse models have been developed which facilitate the transmission of chronic wasting disease (CWD) of cervids and allow prion strain discrimination. The present study was designed to assess the susceptibility of the prototypic mouse line, Tg(CerPrP)1536 ؉/؊ , to bovine spongiform encephalopathy (BSE) prions, which have the ability to overcome species barriers. Tg(CerPrP)1536 ؉/؊ mice challenged with red deer-adapted BSE resulted in 90% to 100% attack rates, and BSE from cattle failed to transmit, indicating agent adaptation in the deer.

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Experimental Chronic Wasting Disease in Wild Type VM Mice

Cited by 18 publications

References 14 publications

Molecular Mechanisms of Chronic Wasting Disease Prion Propagation

Molecular Mechanisms of Chronic Wasting Disease Prion Propagation

Prion replication without host adaptation during interspecies transmissions

Assessing the Susceptibility of Transgenic Mice Overexpressing Deer Prion Protein to Bovine Spongiform Encephalopathy

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