Transmission of Chronic Wasting Disease of Mule Deer to Suffolk Sheep following Intracerebral Inoculation

Hamir, Amir N.; Kunkle, Robert A.; Cutlip, Randall C.; Miller, Janice M.; Williams, Elizabeth; Richt, Jüergen A.

doi:10.1177/104063870601800606

Cited by 82 publications

(81 citation statements)

References 16 publications

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“…The phenotype observed, notably the absence of spongiform changes, makes the disease distinguishable from other TSE in cattle [88]. Eight Suffolk lambs showing various genotypes -four ARQ/ARR, three ARQ/ARQ, one ARQ/VRQ at codons 136, 154, and 171, respectively -showed intermediate susceptibility [87]. Only one (ARQ/VRQ) had a clinical disease, and another a subclinical one (ARQ/ARQ), suggesting a role of the host genotype as for scrapie.…”

Section: Potential Of Interspecies Transmission Of Cwdmentioning

confidence: 98%

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: Potential Of Interspecies Transmission Of Cwdmentioning

confidence: 98%

Prion agent diversity and species barrier

2008

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“…However, sheep and cattle appear to be poorly susceptible to mule deer CWD: ic inoculation with mule deer CWD succeeded to infect only 2 of 8 sheep [28]. Likewise, cattle have note proven to be infected after six years of co-grazing with CWD-infected mule deer, or six years following a direct oral exposure (six years post-inoculation) (M. Miller, personal communication).…”

Section: Interspecies Cwd Transmissionmentioning

confidence: 99%

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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“…Transgenic mice overexpressing bovine or ovine PrP completely resisted infection to 9 different CWD isolates (58), and WT mice do not develop clinical prion disease after infection with elk CWD or hamster 263K scrapie (57,58,60). Furthermore, cattle and sheep are poorly infectible with mule deer CWD, since few animals develop disease after prolonged ips of 6 years, and only after intracerebral inoculation (83,84). Among 170N animals, prions are also transmissible, as elk CWD is infectious to hamsters (85), albeit not very efficiently.…”

Section: Figurementioning

confidence: 99%

A molecular switch controls interspecies prion disease transmission in mice

Sigurdson¹,

Nilsson²,

Hornemann³

et al. 2010

J. Clin. Invest.

129

139

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Transmissible spongiform encephalopathies are lethal neurodegenerative disorders that present with aggregated forms of the cellular prion protein (PrP C ), which are known as PrP Sc . Prions from different species vary considerably in their transmissibility to xenogeneic hosts. The variable transmission barriers depend on sequence differences between incoming PrP Sc and host PrP C and additionally, on strain-dependent conformational properties of PrP Sc . The β 2 -α 2 loop region within PrP C varies substantially between species, with its structure being influenced by the residue types in the 2 amino acid sequence positions 170 (most commonly S or N) and 174 (N or T). In this study, we inoculated prions from 5 different species into transgenic mice expressing either disordered-loop or rigid-loop PrP C variants. Similar β 2 -α 2 loop structures correlated with efficient transmission, whereas dissimilar loops correlated with strong transmission barriers. We then classified literature data on cross-species transmission according to the 170S/N polymorphism. Transmission barriers were generally low between species with the same amino acid residue in position 170 and high between those with different residues. These findings point to a triggering role of the local β 2 -α 2 loop structure for prion transmissibility between different species.

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Transmission of Chronic Wasting Disease of Mule Deer to Suffolk Sheep following Intracerebral Inoculation

Cited by 82 publications

References 16 publications

Prion agent diversity and species barrier

Prion agent diversity and species barrier

A prion disease of cervids: Chronic wasting disease

A molecular switch controls interspecies prion disease transmission in mice

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