Primary Isolation of the Bovine Spongiform Encephalopathy Agent in Mice: Agent Definition based on a Review of 150 Transmissions

Green, R.; Horrocks, Claire; Wilkinson, A G; Hawkins, S. A. C.; Ryder, Stephen

doi:10.1016/j.jcpa.2004.08.002

Cited by 56 publications

(71 citation statements)

References 18 publications

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“…In accordance with our predictions, prions are readily transmitted within 170S mammals: sheep scrapie prions infect cattle (72)(73)(74) and mice (75,76), and cattle BSE prions readily infect sheep (77-79) and mice (14,80). BSE (170S) has also been transmitted to other 170S species, including greater kudu, nyala, eland, scimitar-horned oryx, bison, rhesus macaque, domestic cat, and mink (13,16,81,82).…”

Section: Figuresupporting

confidence: 86%

A molecular switch controls interspecies prion disease transmission in mice

Sigurdson¹,

Nilsson²,

Hornemann³

et al. 2010

J. Clin. Invest.

130

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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Section: Figuresupporting

confidence: 86%

A molecular switch controls interspecies prion disease transmission in mice

Sigurdson¹,

Nilsson²,

Hornemann³

et al. 2010

J. Clin. Invest.

130

139

View full text Add to dashboard Cite

show abstract

“…11 On the other hand, many TSE strains have been detected in small ruminants. Bioassays are lengthy (the mean incubation period for BSE in RIII mice is 408 days) 37 and labor intensive, and results are not always easy to interpret. Additionally, there is a species barrier to infection, which means that not all isolates will necessarily infect an experimental host.…”

Section: Strain Discriminatory and Typing Methodsmentioning

confidence: 99%

Diagnosis of Transmissible Spongiform Encephalopathies in Animals: A Review

Gavier‐Widén

Stack

Baron³

et al. 2005

J VET Diagn Invest

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Abstract. Transmissible spongiform encephalopathies (TSEs) in animals include, among others, bovine spongiform encephalopathy (BSE), scrapie, chronic wasting disease, and atypical forms of prion diseases. Diagnosis of TSEs is based on identification of characteristic lesions or on detection of the abnormal prion proteins in tissues, often by use of their partial proteinase K resistance property. Correctly sampling of target tissues is of utmost importance as this has a considerable effect on test sensitivity. Most of the rapid or screening tests are based on ELISA or Western immunoblot (WB) analysis, and many are officially approved. Confirmatory testing is normally performed by use of histologic examination, immunohistochemical analysis, certain WB protocols, or detection of prion fibrils by use of electron microscopy (scrapie-associated fibril). The discriminatory methods for diagnostic use are mostly based on WB technology and provide initial identification of the prion strain, particularly for differentiation of BSE from scrapie in small ruminants. Definitive prion strain characterization is performed by use of bioassays, usually in mice. A burgeoning number of transgenic mice have been developed for TSE studies. Development of new tests with higher sensitivity and of more reliable diagnostic applications for live animals tested for food safety reasons is a rapidly developing field. Ultimately, the choice of a test for TSE diagnosis depends on the rationale for the testing.

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“…In initial studies, transmission of various sources of infected cattle to a panel of inbred mice expressing the a or b mouse PrP allele (see section 3.4.1) suggested that cattle have been infected by a single strain since incubation periods and distribution of spongiosis in the brain were uniform in each genotype, unlike that seen with scrapie or CJD isolates [31,35,83]. The two agents propagated on a and b genotypes were termed 301C and 301V, respectively (Tab.…”

Section: Conservation Of Strain Phenotypementioning

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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Primary Isolation of the Bovine Spongiform Encephalopathy Agent in Mice: Agent Definition based on a Review of 150 Transmissions

Cited by 56 publications

References 18 publications

A molecular switch controls interspecies prion disease transmission in mice

A molecular switch controls interspecies prion disease transmission in mice

Diagnosis of Transmissible Spongiform Encephalopathies in Animals: A Review

Prion agent diversity and species barrier

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