Inactivation of the Scrapie Agent by Near Monochromatic Ultraviolet Light

Latarjet, R; Muel, B.; Haig, D.A.; Clarke, Martin; Alper, Tikvah

doi:10.1038/2271341a0

Cited by 127 publications

(49 citation statements)

References 18 publications

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“…The differences in the inactivation profiles of prions and viruses provided the first clues that the scrapie agent was not a slow virus as had been widely thought (6,23,41,48,58,59,80).…”

Section: Discussionmentioning

confidence: 99%

Inactivation of Prions by Acidic Sodium Dodecyl Sulfate

Peretz

Supattapone

Giles

et al. 2006

J Virol

116

131

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. 75:3453-3461, 2001), we investigated the inactivation of prions by sodium dodecyl sulfate (SDS) in weak acid. As judged by sensitivity to proteolytic digestion, the diseasecausing prion protein (PrP Sc ) was denatured at room temperature by SDS at pH values of <4.5 or >10. Exposure of Sc237 prions in Syrian hamster brain homogenates to 1% SDS and 0.5% AcOH at room temperature resulted in a reduction of prion titer by a factor of ca. 10 7 ; however, all of the bioassay hamsters eventually developed prion disease. When various concentrations of SDS and AcOH were tested, the duration and temperature of exposure acted synergistically to inactivate both hamster Sc237 prions and human sporadic Creutzfeldt-Jakob disease (sCJD) prions. The inactivation of prions in brain homogenates and those bound to stainless steel wires was evaluated by using bioassays in transgenic mice. sCJD prions were more than 100,000 times more resistant to inactivation than Sc237 prions, demonstrating that inactivation procedures validated on rodent prions cannot be extrapolated to inactivation of human prions. Some procedures that significantly reduced prion titers in brain homogenates had a limited effect on prions bound to the surface of stainless steel wires. Using acidic SDS combined with autoclaving for 15 min, human sCJD prions bound to stainless steel wires were eliminated. Our findings form the basis for a noncorrosive system that is suitable for inactivating prions on surgical instruments, as well as on other medical and dental equipment.

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“…The differences in the inactivation profiles of prions and viruses provided the first clues that the scrapie agent was not a slow virus as had been widely thought (6,23,41,48,58,59,80).…”

Section: Discussionmentioning

confidence: 99%

Inactivation of Prions by Acidic Sodium Dodecyl Sulfate

Peretz

Supattapone

Giles

et al. 2006

J Virol

116

131

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“…Transmission of scrapie to mice ushered in the application of biochemical experimentation aimed at revealing the composition of the infectious pathogen (14,53). The startling results of ionizing and UV irradiation studies performed on mouse brain homogenates intensified the search for the nucleic acid genome of the putative "virus" causing scrapie (3,4,35). Those studies argued that the scrapie agent does not contain a nucleic acid, because it is extremely resistant to inactivation by irradiation at 254 nm and its target size, determined by ionizing radiation, is less than 150 kDa.…”

Section: Discussionmentioning

confidence: 99%

Search for a Prion-Specific Nucleic Acid

Safar

Kellings

Serban

et al. 2005

J Virol

121

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Diversity of prion strains was attributed to an elusive nucleic acid, yet a search spanning nearly two decades has failed to identify a prion-specific polynucleotide. In our search for a prion-specific nucleic acid, we analyzed nucleic acids in purified fractions from the brains of Syrian hamsters infected with Sc237 prions. Purification of Sc237 prions removed nucleic acids larger than 50 nucleotides as measured by return refocusing electrophoresis (RRGE). To determine the size of the largest polynucleotide present in purified fractions at an abundance of one molecule per infectious (ID 50 ) unit, we measured prions present after inoculation. In order to account for the rapid clearance of prions after intracerebral inoculation, we determined the number of PrP Sc molecules and ID 50 units of prions that were retained in brain. Factoring in clearance after inoculation, we estimate that the largest polynucleotide present in our purified fractions at one molecule per ID 50 unit is Ϸ25 nucleotides in length. In the same fractions, there were Ϸ3,000 protease-resistant PrP Sc molecules per ID 50 unit after accounting for clearance of PrP Sc following inoculation. We compared the resistance of Sc237 and 139H prions to inactivation by UV irradiation at 254 nm. Irradiation of homogenates and microsomes diminished prion infectivity by a factor of Ϸ1,000 but did not alter the strain-specified properties of the Sc237 and 139H prions. The data reported here combined with the production of synthetic prions argue that the 25-mer polynucleotides found in purified prion preparations are likely to be host encoded and of variable sequence; additionally, these 25-mers are unlikely to be prion specific.

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“…3 M GdnSCN) that modify the structure of PrP 27-30 also inactivate prion infectivity (25). In contrast, prion infectivity resists inactivation by reagents that disrupt nucleic acid polymers including nucleases, psoralens, and UV irradiation (50,(59)(60)(61)(62)(63). Microsequencing of the N-terminus of PrP 27-30 (54) led to the cloning and sequencing of the PrP gene (38,55 The N-terminus of PrP 27-30 corresponds to approximately codon 90 in the full-length coding sequence (57,64).…”

Section: Biochemical Characterizationmentioning

confidence: 99%

Pathologic Conformations of Prion Proteins

Cohen

Prusiner

1998

Annu. Rev. Biochem.

492

379

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While many aspects of prion disease biology are unorthodox, perhaps the most fundamental paradox is posed by the coexistence of inherited, sporadic, and infectious forms of these diseases. Sensible molecular mechanisms for prion propagation must explain all three forms of prion diseases in a manner that is compatible with the formidable array of experimental data derived from histopathological, biochemical, biophysical, human genetic, and transgenetic studies. In this review, we explore prion disease pathogenesis initially from the perspective of an autosomal dominant inherited disease. Subsequently, we examine how an intrinsically inherited disease could present in sporadic and infectious forms. Finally, we explore the phenomenologic constraints on models of prion replication with a specific emphasis on biophysical studies of prion protein structures. CONTENTS

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Inactivation of the Scrapie Agent by Near Monochromatic Ultraviolet Light

Cited by 127 publications

References 18 publications

Inactivation of Prions by Acidic Sodium Dodecyl Sulfate

Inactivation of Prions by Acidic Sodium Dodecyl Sulfate

Search for a Prion-Specific Nucleic Acid

Pathologic Conformations of Prion Proteins

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