Prions in Skeletal Muscles of Deer with Chronic Wasting Disease

Angers, Rachel; Browning, Shawn; Seward, Tanya; Sigurdson, Christina J.; Miller, Michael W.; Hoover, Edward A.; Telling, Glenn C.

doi:10.1126/science.1122864

Cited by 203 publications

(157 citation statements)

References 7 publications

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“…At variance with scrapie, the placenta is poorly infectious, suggesting that transmission from mother-to-lamb might be rather low [135]. The CWD agent has a pronounced tropism for lymphoid tissues and muscles are infectious [3,178]. Thus CWD is today taken as seriously as BSE in Europe by health authorities.…”

Section: Strain Diversity In Cwd?mentioning

confidence: 99%

Prion agent diversity and species barrier

2008

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-Mammalian prions are the infectious agents responsible for transmissible spongiform encephalopathies (TSE), a group of fatal, neurodegenerative diseases, affecting both domestic animals and humans. The most widely accepted view to date is that these agents lack a nucleic acid genome and consist primarily of PrP Sc , a misfolded, aggregated form of the host-encoded cellular prion protein (PrP C ) that propagates by autocatalytic conversion and accumulates mainly in the brain. The BSE epizooty, allied with the emergence of its human counterpart, variant CJD, has focused much attention on two characteristics that prions share with conventional infectious agents. First, the existence of multiple prion strains that impose, after inoculation in the same host, specific and stable phenotypic traits such as incubation period, molecular pattern of PrP Sc and neuropathology. Prion strains are thought to be enciphered within distinct PrP Sc conformers. Second, a transmission barrier exists that restricts the propagation of prions between different species. Here we discuss the possible situations resulting from the confrontation between species barrier and prion strain diversity, the molecular mechanisms involved and the potential of interspecies transmission of animal prions, including recently discovered forms of TSE in ruminants.prion / strain / misfolding / species barrier / PrP Table of Mammalian prion diseases or transmissible spongiform encephalopathies (TSE) form a group of related, invariably fatal neurodegenerative disorders of both animals and humans. The brain pathology consists of spongiosis, astrocytosis, neuronal loss and neural tissue from affected individuals contains an infectious agent, the prion, setting these diseases apart from other neurodegenerative diseases. Prion replication is thought to involve in essence the self-perpetuating conversion of the host-encoded cellular prion protein (PrP C ) into a misfolded form (PrP Sc ) that tends to aggregate and may be neurotoxic (for reviews [1,157]). Prion replication may also occur in lymphoid tissues but is there poorly if not pathogenic (for review [126], [133]). PrP C is a protein with two variably occupied glycosylation sites. It is attached at the outer of the plasma membrane by a glycosylphosphatidylinositol anchor. Its secondary structure is rich in alpha-helix and the protein is likely to be in a monomeric state in mild detergents. While its precise physiological function has not been assigned, PrP C is essential for prion replication and neurotoxicity to occur [57,129]. Upon infection, PrP C is refolded -without apparent post-translational modification -into beta-sheet -rich PrP Sc , initially in the presence of exogenous PrP Sc and then by an autocatalytic process. It leads to the formation of aggregates, sometimes of amyloid type, that can be differentiated from PrP C because of their partial resistance to protease digestion and of their insolubility into non-denaturing detergents [153]. Proteinase K, the most commonly used protease, di...

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Section: Strain Diversity In Cwd?mentioning

confidence: 99%

Prion agent diversity and species barrier

2008

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“…In addition to lymphoid tissues, PrP Sc or infectivity has been detected in other non-CNS tissues, including pancreas [17,77], adrenal gland [17,77], and skeletal muscle [2]. Recently PrP Sc was described in cardiac muscle from 7 of 16 (44%) white-tailed deer and from 12 of 17 (71%) elk [35].…”

Section: Cwd Prion Spread and Target Organsmentioning

confidence: 99%

“…Skeletal muscle has been shown to harbor CWD prion infectivity [2], underscoring that other species will almost certainly be exposed to CWD through feeding. However, CWD has not been successfully transmitted by oral inoculation to species outside of the cervid family, suggestive of a strong species barrier for heterologous PrP conversion.…”

Section: Interspecies Cwd Transmissionmentioning

confidence: 99%

“…Millions of North Americans hunt deer and elk (US Department of the Interior, Census Bureau), and there is no doubt that people have been exposed to CWD through venison consumption, particularly in light of recent data showing CWD prions in muscle [2]. Human susceptibility to CWD or to other newly emerging animal TSE [9,14] is still unclear, although we can be somewhat reassured in that there have been no large scale outbreaks of human TSE cases in Colorado and Wyoming, where CWD has existed for decades [51].…”

Section: Human Susceptibility To Cwdmentioning

confidence: 99%

“…Browning et al developed the first transgenic mouse expressing cervid PrP [10], which was subsequently utilized as a bioassay to detect CWD prions in muscle [2]. Several transgenic mice expressing cervid PrP have since been produced using different constructs and sequences [10,41,44,52,84] (detailed in Tab.…”

Section: Tools For Cwd Research: Cell Lines and Cervid Prp Expressingmentioning

confidence: 99%

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A prion disease of cervids: Chronic wasting disease

2008

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-Chronic wasting disease (CWD) is a prion disease of deer, elk, and moose, initially recognized in Colorado mule deer. The discovery of CWD beyond the borders of Colorado and Wyoming, in Canada and as far east as New York, has led to its emergence as a prion disease of international importance. Epidemiological studies indicate that CWD is horizontally transmitted among free-ranging animals, potentially indirectly by prion-containing secreta or excreta contaminating the environment. Experimental CWD transmission attempts to other wild and domestic mammals and to transgenic mice expressing the prion protein of cattle, sheep, and humans have shed light on CWD species barriers. Transgenic mice expressing the cervid prion protein have proven useful for assessing the genetic influences of Prnp polymorphisms on CWD susceptibility. Accumulating evidence of CWD pathogenesis indicates that the misfolded prion protein or prion infectivity seems to be widely disseminated in many nonneural organs and in blood. This review highlights contemporary research findings in this prion disease of free-ranging wildlife.

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Colorado Surveillance Program for Chronic Wasting Disease Transmission to Humans

Anderson¹,

Bosque²,

Filley³

et al. 2007

Arch Neurol

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To describe 2 patients with rapidly progressive dementia and risk factors for exposure to chronic wasting disease (CWD) in whom extensive testing negated the possible transmission of CWD.Design/Methods: We describe the evaluation of 2 young adults with initial exposure histories and clinical presentations that suggested the possibility of CWD transmission to humans.Patients: A 52-year-old woman with possible laboratory exposure to CWD and a 25-year-old man who had consumed meat from a CWD endemic area.

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Prions in Skeletal Muscles of Deer with Chronic Wasting Disease

Cited by 203 publications

References 7 publications

Prion agent diversity and species barrier

Prion agent diversity and species barrier

A prion disease of cervids: Chronic wasting disease

Colorado Surveillance Program for Chronic Wasting Disease Transmission to Humans

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