The exceptionally small size of the scrapie agent

Alper, Tikvah; Haig, D.A.; Clarke, Martin

doi:10.1016/0006-291x(66)90478-5

Cited by 364 publications

(148 citation statements)

References 15 publications

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“…The high resistance of TSE agents to conventional methods of chemical or thermal inactivation and to UV or ionizing radiation (Alper et al, 1966(Alper et al, , 1967Brown et al, 1982Brown et al, , 1986Kimberlin et al, 1983;Taguchi et al, 1991;Tateishi et al, 1991;Ernst & Race, 1993;Taylor et al, 1994;Manuelidis, 1997;Taylor, 1999; for review see Taylor, 2000), as well as their high binding affinity to and tenacity on steel surfaces (Zobeley et al, 1999;Flechsig et al, 2001), warrant specific decontamination procedures in the reprocessing of surgical instruments (Rutala & Weber, 2001). Treatments that are considered appropriate for decontamination include use of 1-2 M NaOH solution (for 24 h), 2?5-5 % NaOCl solution (for 24 h) as well as 3, 4 or 6 M GdnSCN solution (for 24 h, 1 h or 15 min, respectively), followed by steam sterilization at 134 u C for 18 min to 1 h (Simon & Pauli, 1998;World Health Organization, 1999;Hörnlimann et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Decontamination of surgical instruments from prion proteins: in vitro studies on the detachment, destabilization and degradation of PrPSc bound to steel surfaces

Lemmer

Mielke

Pauli

et al. 2004

Journal of General Virology

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Effective reprocessing of surgical instruments ensuring elimination of inadvertent contamination with infectious agents causing transmissible spongiform encephalopathies (TSEs) is essential for the prevention of iatrogenic transmission of Creutzfeldt-Jakob disease (CJD) or its new variant (vCJD) from asymptomatic carriers. In a search for effective yet instrument-friendly and routinely applicable reprocessing procedures, we used an in vitro carrier assay to assess the decontamination activity exerted by different reagents on pathological prion protein (PrP Sc ), the biochemical marker for TSE infectivity, attached to steel surfaces. In this assay, steel wires were contaminated with 263K scrapie brain homogenate and reprocessed for decontamination by exposure to several different test reagents. Residual contamination with PrP Sc and its protease-resistant core PrP27-30, still present after reprocessing on the wire surface or in the cleaning solution, was monitored by sensitive Western blot detection without or after proteinase K digestion. Using this approach, various reagents and processing conditions were screened for both their efficacy of decontamination and their active principles, such as detachment, destabilization or degradation of surface-bound prion protein. This revealed that, under appropriate conditions, relatively mild reagents such as 0?2 % SDS/0?3 % NaOH (pH 12?8), a commercially available alkaline cleaner (pH 11?9-12?2), a disinfectant containing 0?2 % peracetic acid and low concentrations of NaOH (pH 8?9) or 5 % SDS (pH 7?1) exert potent decontaminating activities on PrP Sc /PrP27-30 attached to steel surfaces. For in vivo validation, wires reprocessed in these reagents have been implanted into reporter animals in ongoing experiments.

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Section: Introductionmentioning

confidence: 99%

Decontamination of surgical instruments from prion proteins: in vitro studies on the detachment, destabilization and degradation of PrPSc bound to steel surfaces

Lemmer

Mielke

Pauli

et al. 2004

Journal of General Virology

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“…Most investigations have been done with scrapie, with material purified from the brains of hamsters and other laboratory animals (Prusiner et al, 1980aMcKinley et al, 1986). These have shown survival of scrapie agent after autoclaving at 121°C for up to 1 h (Brown et al, 1982a(Brown et al, , 1986, survival in formaldehyde 8% w/v (Pattison, 1965;Brown et af., 19826), and alcohol 70% v/v (Prusiner, 1982), inactivation by phenol Prusiner et al, 1980a), and a high degree of resistance to ultra-violet light and to ionising radiation (Alper et al, 1966(Alper et al, , 1967Gibbs et af., 1978). A fuller comparison of the properties of IFDO and slow viruses is listed in table V. This reveals many similarities between IFDO and the agents of Creutzfeldt-Jakob disease and scrapie.…”

Section: Discussionmentioning

confidence: 99%

A novel replicating agent isolated from the human intestinal tract having characteristics shared with Creutzfeldt-Jakob and related agents

Burdon

1989

Journal of Medical Microbiology

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Summary.A novel replicating agent (IFDO) was isolated from ileal fluid. Growth occurred in vitro under aerobic and anaerobic conditions, and was faster at 37°C than at room temperature. The doubling time was 1543 min. Colonies were dark brown in colour and occurred beneath the surface of agar after conventional surface inoculation. Provisional data indicate that the agent may be a normal intestinal commensal. The agent was remarkably resistant to inactivation by steam at 134"C, formaldehyde and glutaraldehyde; it was relatively resistant to ionising radiation, and it was filterable through membranes with a nominal pore diameter of 10 nm. Such properties, with the exception of growth in cell-free medium, are shared by "unconventional agents" such as those of Creutzfeldt-Jakob disease and scrapie. Further comparison of the properties of the intestinal agent and of slow viruses revealed additional shared characteristics, including resistance to proteinase K and trypsin, and inactivation by guanidine thiocyanate, diethyl pyrocarbonate, phenol and sodium hydroxide. The agent differs from that of scrapie in being inactivated by ethidium bromide, zinc nitrate, EDTA, hydroxylamine in the presence Sarkosyl, and, under certain circumstances, by ribonuclease. Broth cultures of the agent contained particles possessing considerable size heterogeneity. The smaller filterable particles were generally more susceptible to inactivation, did not survive autoclaving, and were inactivated by papaya protease and lipase. It is possible that the replicating agent may be formed by crystallisation from constituents of the medium, and not by a biological process. This does not exclude the postulated relationship to slow viruses.

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“…wt. estimated to be 1.5 x 105 to 0.6 × 105; Alper et al, 1966;Latarjet, 1979); since the transfection procedures are based on the ability of the nucleic acid to easily penetrate the ceil, it seems logical to think that scrapie nucleic acid would enter more readily. Although it was shown that biological activity of the ~X174 virus comes through the extraction procedure employed and the brain cell cultures were capable of being transfected, nucleic acid from highly infectious scrapie tissues still proved noninfectious.…”

Section: Discussionmentioning

confidence: 99%

“…The non-nucleic acid scrapie theory has been suggested since 1959 from several authors based on different properties (Stamp et al, 1959;Field, 1966;Alper et al, 1966Alper et al, , 1967Alper et al, , 1978Gibbons & Hunter, 1967). Although, at present, it is difficult to conceive a replicating molecule other than a nucleic acid, the possibility of new forms of replication must remain open.…”

Section: Discussionmentioning

confidence: 99%

“…Their unusual resistance to heat (Hunter & Millson, 1964;Haig & Clarke, 1965;Gibbs, 1967;Mould & Dawson, 1970), enzyme degradation (Hunter et al, 1976;Prusiner et al, 1980b) and inactivation by u.v. and ionizing radiation (Alper et al, 1966;Gibbs et al, 1978); their apparent failure to induce a detectable immune response (Porter et aL, 1973;Kingsbury et aL, 1981), cytopathological changes in cells in vitro, or its poor replication when inoculated into established tissue cultures (Clarke, 1979), have formed the basis for their being characterized as the 'unconventional viruses'. Since several of these properties are similar to those of the plant viroids, it has been suggested that scrapie may be a viroid of animals (Diener, 1972;Malone et al, 1979); however, unlike the plant viroids a specific nucleic acid has not, as yet, been demonstrated for any of the unconventional viruses.…”

Section: Introductionmentioning

confidence: 99%

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Inability to Transmit Scrapie by Transfection of Mouse Embryo Cells in vitro

Dt²,

et al. 1982

Journal of General Virology

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SUMMARYInfectivity of nucleic acid from highly infectious mouse scrapie brains was studied by transfecting the nucleic acid in vitro prior to inoculation into animals. Foetal mouse brain and whole mouse embryo cultures were chosen as the cells used for the transfection. As an internal control, infectious nucleic acid was recovered from bacteriophage ~X174 and whole virus particles were obtained when cultures were transfected with herpes simplex virus DNA. In contrast, none of the animals inoculated with nucleic acid preparations derived from scrapie-infected tissues developed scrapie disease either with or without transfection procedures. These findings (i) show transfection techniques fail to elicit evidence of a scrapie-specific infectious nucleic acid and (ii) confirm the observation that scrapie is not a viroid.

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The exceptionally small size of the scrapie agent

Cited by 364 publications

References 15 publications

Decontamination of surgical instruments from prion proteins: in vitro studies on the detachment, destabilization and degradation of PrPSc bound to steel surfaces

Decontamination of surgical instruments from prion proteins: in vitro studies on the detachment, destabilization and degradation of PrPSc bound to steel surfaces

A novel replicating agent isolated from the human intestinal tract having characteristics shared with Creutzfeldt-Jakob and related agents

Inability to Transmit Scrapie by Transfection of Mouse Embryo Cells in vitro

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