Discriminating Scrapie and Bovine Spongiform Encephalopathy Isolates by Infrared Spectroscopy of Pathological Prion Protein

Thomzig, Achim; Spassov, Sashko; Friedrich, Manuela; Naumann, Dieter; Beekes, Michael

doi:10.1074/jbc.m403730200

Cited by 71 publications

(71 citation statements)

References 46 publications

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“…In the past several years considerable evidence has accumulated indicating that prion strains do, indeed, exhibit notable differences in the amount and type of ␤-sheet structure, conformational stability, proteolytic resistance, and surface-exposed epitopes (2)(3)(4)(5)(6)(7). Although the results of these aforementioned studies were consistent with the protein-only hypothesis, the primary origin of strain-specific conformational variations remains unclear.…”

supporting

confidence: 61%

The Same Primary Structure of the Prion Protein Yields Two Distinct Self-propagating States

Makarava

Baskakov

2008

Journal of Biological Chemistry

109

133

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The question of whether distinct self-propagating structures could be formed within the same amino acid sequence in the absence of external cofactors or templates has important implications for a number of issues, including the origin of prion strains and the engineering of smart, self-assembling peptidebased biomaterials. In the current study, we showed that chemically identical prion protein can give rise to conformationally distinct, self-propagating amyloid structures in the absence of cellular cofactors, post-translational modification, or PrP Scspecified templates. Even more surprising, two self-replicating states were produced under identical solvent conditions, but under different shaking modes. Individual prion conformations were inherited by daughter fibrils in seeding experiments conducted under alternative shaking modes, illustrating the high fidelity of fibrillation reactions. Our study showed that the ability to acquire conformationally different self-propagating structures is an intrinsic ability of protein fibrillation and strongly supports the hypothesis that conformational variation in selfpropagating protein states underlies prion strain diversity.The existence of multiple prion strains is considered to be one of the most puzzling features of prion biology. According to the protein-only hypothesis of prion propagation, the normal cellular isoform of the prion protein, PrP C , can be converted into a range of self-propagating disease-related structures, referred to as strains of PrP Sc (1). Although certain physical properties are common for all PrP Sc strains, each strain also possesses unique strain-specific conformational features. Within the protein-only hypothesis, it is assumed that variation in PrP Sc structure can give rise to a broad range of strain-specific disease phenotypes, including substantial variation in incubation time to disease, in pathology, and in behavioral symptoms.In the past several years considerable evidence has accumulated indicating that prion strains do, indeed, exhibit notable differences in the amount and type of ␤-sheet structure, conformational stability, proteolytic resistance, and surface-exposed epitopes (2-7). Although the results of these aforementioned studies were consistent with the protein-only hypothesis, the primary origin of strain-specific conformational variations remains unclear. What is the possible source of strain-specific structural variation in PrP Sc ? A "unified theory" of prion propagation postulates that the strain-specific features of the prion infectious agent may be encoded by a coprion, or small nucleic acid (8). Alternatively, the ability to adopt multiple self-propagating structures may be an intrinsic property of the fibrillation reaction itself and can be achieved in the absence of a coprion. In the past, two distinct amyloid states were produced from chemically identical A␤ peptides (9); however, this property has never been demonstrated for fibrillation of larger polypeptides or global proteins such as PrP.In the current study...

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supporting

confidence: 61%

The Same Primary Structure of the Prion Protein Yields Two Distinct Self-propagating States

Makarava

Baskakov

2008

Journal of Biological Chemistry

109

133

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“…This preferential involvement of rostral brain regions in L-type BSE has also been described in cattle ( 13 ) and on transmission into bovine transgenic mice ( 18 , 24 ). Transmission of TME or typical BSE into wild-type mice ( 31 , 32 ) or hamsters ( 33 , 34 ) also resulted in distinct transmissibility between these TSEs in these host species. Based on these findings, we conclude that typical BSE is not a likely source for TME in mink; however, if TME were to be due to infection with a cattle TSE, the most likely candidate is L-type BSE.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model

Baron

Bencsik

Biacabe

et al. 2007

Emerg. Infect. Dis.

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“…It was reported that this approach is sensitive and specific (97% and 100% respectively) but it was not known whether the changes detected by FTIR were specific to TSEs or whether they were due to bacterial, viral, fungal or parasitic micro-organisms. Analysis by FTIR has proved useful for discriminating between scrapie and BSE pathological PrP strains [112], identifying protein structural changes in nerve ganglia of infected hamsters [56], and brain tissue of TSE infected animals [54,55].…”

Section: Mid-infrared Spectroscopymentioning

confidence: 99%

The use of non-prion biomarkers for the diagnosis of Transmissible Spongiform Encephalopathies in the live animal

Parveen

Moorby²,

Allison³

et al. 2005

Vet. Res.

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-Scrapie and bovine spongiform encephalopathy (BSE) are major global concerns and the emergence of variant Creutzfeldt-Jakob disease (vCJD) has caused turmoil for blood transfusion services and hospitals worldwide. Recent reports of iatrogenic CJD (iCJD) cases following blood transfusions from Transmissible Spongiform Encephalopathies (TSE)-infected donors have fuelled this concern. Major diagnostic tests for BSE and scrapie are conducted post-mortem from animals in late stages of the disease. Although the lymphoreticular system is involved in the earlier pathogenesis of some forms of sheep scrapie and vCJD, which presents great opportunity for diagnostic development, other TSE diseases (some strains of scrapie, sporadic CJD (sCJD) and bovine BSE) do not present such a diagnostic opportunity. Thus, there is an urgent need for premortem tests that differentiate between healthy and diseased individuals at early stages of illness, in accessible samples such as blood and urine using less invasive procedures. This review reports on the current state of progress in the development and use of prion and non-prion biomarkers in the diagnosis of TSE diseases. Some of these efforts have concentrated on improving the sensitivity of PrP Sc detection to allow in vivo diagnosis at low abundances of PrP Sc whilst others have sought to identify non-prion protein biomarkers of TSE disease, many of which are still at early stages of development. In this review we comment upon the limitations of prion based tests and review current research on the development of tests for TSE that rely on non-prion disease markers in body fluids that may allow preclinical disease diagnosis.

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Discriminating Scrapie and Bovine Spongiform Encephalopathy Isolates by Infrared Spectroscopy of Pathological Prion Protein

Cited by 71 publications

References 46 publications

The Same Primary Structure of the Prion Protein Yields Two Distinct Self-propagating States

The Same Primary Structure of the Prion Protein Yields Two Distinct Self-propagating States

Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model

The use of non-prion biomarkers for the diagnosis of Transmissible Spongiform Encephalopathies in the live animal

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