Identification of two biologically distinct strains of transmissible mink encephalopathy in hamsters

Bessen, Richard A.; Marsh, Richard F.

doi:10.1099/0022-1317-73-2-329

Cited by 268 publications

(232 citation statements)

References 30 publications

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“…Sc237 prions were passaged intracerebrally through SHa as described (32). The DY prion strain was a gift from Richard Marsh (University of Wisconsin, Madison, WI) and was passaged through SHa (33).…”

Section: Methodsmentioning

confidence: 99%

Prion detection by an amyloid seeding assay

Colby

Zhang²,

Wang³

et al. 2007

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

208

185

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Polymerization of recombinant prion protein (recPrP), which was produced in bacteria, into amyloid fibers was accompanied by the acquisition of prion infectivity. We report here that partially purified preparations of prions seed the polymerization of recPrP into amyloid as detected by a fluorescence shift in the dye Thioflavin T. Our amyloid seeding assay (ASA) detected PrP Sc , the sole component of the prion, in brain samples from humans with sporadic Creutzfeldt–Jakob disease, as well as in rodents with experimental prion disease. The ASA detected a variety of prion strains passaged in both mice and hamsters. The sensitivity of the ASA varied with strain type; for hamster Sc237 prions, the limit of detection was ≈1 fg. Some prion strains consist largely of protease-sensitive PrP Sc (sPrP Sc ), and these strains were readily detected by ASA. Our studies show that the ASA provides an alternative methodology for detecting both sPrP Sc and protease-resistant PrP Sc that does not rely on protease digestion or immunodetection.

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Section: Methodsmentioning

confidence: 99%

Prion detection by an amyloid seeding assay

Colby

Zhang²,

Wang³

et al. 2007

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

208

185

View full text Add to dashboard Cite

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“…This had also been described for strains isolated in hamster from transmissible mink encephalopathy (7)(8)(9)(10). Criteria showing the molecular diversity of PrP res include ratios of the di-, mono-, and unglycosylated forms, their respective molecular masses, and the long-term resistance of the protein to proteinase K digestion.…”

mentioning

confidence: 77%

Molecular Analysis of the Protease-Resistant Prion Protein in Scrapie and Bovine Spongiform Encephalopathy Transmitted to Ovine Transgenic and Wild-Type Mice

Baron¹,

Crozet²,

Biacabe³

et al. 2004

J Virol

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The existence of different strains of infectious agents involved in scrapie, a transmissible spongiform encephalopathy (TSE) of sheep and goats, remains poorly explained. These strains can, however, be differentiated by characteristics of the disease in mice and also by the molecular features of the protease-resistant prion protein (PrP res ) that accumulates into the infected tissues. For further analysis, we first transmitted the disease from brain samples of TSE-infected sheep to ovine transgenic [Tg(OvPrP4)] and to wild-type (C57BL/6) mice. We show that, as in sheep, molecular differences of PrP res detected by Western blotting can differentiate, in both ovine transgenic and wild-type mice, infection by the bovine spongiform encephalopathy (BSE) agent from most scrapie sources. Similarities of an experimental scrapie isolate (CH1641) with BSE were also likewise found following transmission in ovine transgenic mice. Secondly, we transmitted the disease to ovine transgenic mice by inoculation of brain samples of wild-type mice infected with different experimental scrapie strains (C506M3, 87V, 79A, and Chandler) or with BSE. Features of these strains in ovine transgenic mice were reminiscent of those previously described for wild-type mice, by both ratios and by molecular masses of the different PrP res glycoforms. Moreover, these studies revealed the diversity of scrapie strains and their differences with BSE according to labeling by a monoclonal antibody (P4). These data, in an experimental model expressing the prion protein of the host of natural scrapie, further suggest a genuine diversity of TSE infectious agents and emphasize its linkage to the molecular features of the abnormal prion protein.

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“…I, [25]). DY but not HY retained pathogenicity for mink through at least four passages in hamsters, suggesting the possibility that it was the major if not the sole mink pathogen component in the original source [24]. When the Stetsonville isolate was biologically cloned by three transmissions at endpoint dilutions in mink, so as to isolate a single strain from a potential mixture before transmission to hamsters, both HY and DY PrP res patterns were again detected on first passage and both strains could be stably propagated on serial passage [11].…”

Section: Lessons From Studies In Rodent Modelsmentioning

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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Identification of two biologically distinct strains of transmissible mink encephalopathy in hamsters

Cited by 268 publications

References 30 publications

Prion detection by an amyloid seeding assay

Prion detection by an amyloid seeding assay

Molecular Analysis of the Protease-Resistant Prion Protein in Scrapie and Bovine Spongiform Encephalopathy Transmitted to Ovine Transgenic and Wild-Type Mice

Prion agent diversity and species barrier

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