Unusual resistance to ionizing radiation of the viruses of kuru, Creutzfeldt-Jakob disease, and scrapie.

Gibbs, Clarence J.; Gajdusek, D. Carleton; Latarjet, R

doi:10.1073/pnas.75.12.6268

Cited by 111 publications

(30 citation statements)

References 8 publications

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“…60,61 Rather, such modeling studies suggest that small oligomers would function as the most infectious units. 62,63 Consistent with these predictions, ionizing radiation, [64][65][66] fractionation, 67,68 and denaturation 69 studies support a minimum infectious complex of ∼5 PrP subunits, with peak infectivity in the range of 14-28 monomers. 68 Moreover, the threshold behavior of scrapie appearance, in which the sporadic rate of disease is exceedingly low, can only be explained by a mechanism in which multiple, spontaneously arising PrP Sc monomers must come together to form a stable complex that functions as an active template.…”

Section: Regeneration Of the Prion Template In Vivosupporting

confidence: 61%

Prion Propagation: The Role of Protein Dynamics

Pezza

Serio

2007

Prion

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Section: Regeneration Of the Prion Template In Vivosupporting

confidence: 61%

Prion Propagation: The Role of Protein Dynamics

Pezza

Serio

2007

Prion

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“…My fascination with CJD quickly shifted to scrapie once I learned of the remarkable radiobiological data that Tikvah Alper and her colleagues had collected on the scrapie agent (32)(33)(34). The scrapie agent had been found to be extremely resistant to inactivation by UV and ionizing radiation, as was later shown for the CJD agent (35). It seemed to me that the most intriguing question was the chemical nature of the scrapie agent; Alper's data had evoked a torrent of hypotheses concerning its composition.…”

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confidence: 99%

Molecular characterization of proteolytic cleavage sites of the Pseudomonas syringae effector AvrRpt2

Chisholm

Dahlbeck

Krishnamurthy

et al. 2005

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

137

138

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Prions are unprecedented infectious pathogens that cause a group of invariably fatal neurodegenerative diseases by an entirely novel mechanism. Prion diseases may present as genetic, infectious, or sporadic disorders, all of which involve modification of the prion protein (PrP). Bovine spongiform encephalopathy (BSE), scrapie of sheep, and Creutzfeldt-Jakob disease (CJD) of humans are among the most notable prion diseases. Prions are transmissible particles that are devoid of nucleic acid and seem to be composed exclusively of a modified protein (PrP Sc ). The normal, cellular PrP (PrP C ) is converted into PrP Sc through a posttranslational process during which it acquires a high ␤-sheet content. The species of a particular prion is encoded by the sequence of the chromosomal PrP gene of the mammals in which it last replicated. In contrast to pathogens carrying a nucleic acid genome, prions appear to encipher strain-specific properties in the tertiary structure of PrP Sc . Transgenetic studies argue that PrP Sc acts as a template upon which PrP C is refolded into a nascent PrP Sc molecule through a process facilitated by another protein. Miniprions generated in transgenic mice expressing PrP, in which nearly half of the residues were deleted, exhibit unique biological properties and should facilitate structural studies of PrP Sc . While knowledge about prions has profound implications for studies of the structural plasticity of proteins, investigations of prion diseases suggest that new strategies for the prevention and treatment of these disorders may also find application in the more common degenerative diseases.

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“…Defining conditions for inactivation of prions is an important undertaking in view of the human forms of prion disease that were elucidated by studies demonstrating the experimental transmission of prions from patients who died of kuru or CJD to apes and monkeys (26,27). Radiation inactivation of CJD prions and studies of human PrP argue that human prions, like those causing scrapie and BSE, are resistant to inactivation (10,28). More recently, the number of cases of iatrogenic CJD; the transmission of BSE prions from cattle to humans, causing variant (v) CJD (97,98); and the probable transmission of vCJD by blood transfusion (45,55) highlight the pressing need for effective prion decontamination.…”

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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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Unusual resistance to ionizing radiation of the viruses of kuru, Creutzfeldt-Jakob disease, and scrapie.

Abstract: The titers of several preparations of kuru, Creutzfeldt-Jacob disease, and scrapie viruses were reduced by only 1/10th or less by high doses of 'y radiation of 50 kGy and by only I/lOth-1/lOOOth or less for 200 kGy. This unusual ra-

Cited by 111 publications

References 8 publications

Prion Propagation: The Role of Protein Dynamics

Prion Propagation: The Role of Protein Dynamics

Molecular characterization of proteolytic cleavage sites of the Pseudomonas syringae effector AvrRpt2

Inactivation of Prions by Acidic Sodium Dodecyl Sulfate

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