Solvent extraction as an adjunct to rendering: the effect on BSE and scrapie agents of hot solvents followed by dry heat and steam

Taylor, David; Fernie, Karen; McConnell, I.; Ferguson, C. E.; Steele, Philip

doi:10.1136/vr.143.1.6

Cited by 29 publications

(13 citation statements)

References 17 publications

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“…(ii) Prions are more easily inactivated by heat in the presence of fat rather than in water (15). (iii) Polar organic solvents that are able to extract polar lipids such 2-choroethanol inactivate prions, whereas nonpolar solvents such as hexane do not (16,17). (iv) Variations in the strength of interaction between PrP and phospholipids correlate with differences in the thermostability of various prion strains (18,19).…”

Section: Discussionmentioning

confidence: 99%

Isolation of phosphatidylethanolamine as a solitary cofactor for prion formation in the absence of nucleic acids

Deleault

Piro²,

Walsh³

et al. 2012

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

210

236

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Infectious prions containing the pathogenic conformer of the mammalian prion protein (PrP Sc ) can be produced de novo from a mixture of the normal conformer (PrP C ) with RNA and lipid molecules. Recent reconstitution studies indicate that nucleic acids are not required for the propagation of mouse prions in vitro, suggesting the existence of an alternative prion propagation cofactor in brain tissue. However, the identity and functional properties of this unique cofactor are unknown. Here, we show by purification and reconstitution that the molecule responsible for the nucleaseresistant cofactor activity in brain is endogenous phosphatidylethanolamine (PE). Synthetic PE alone facilitates conversion of purified recombinant (rec)PrP substrate into infectious recPrP Sc molecules. Other phospholipids, including phosphatidylcholine, phosphatidylserine, phosphatidylinositol, and phosphatidylglycerol, were unable to facilitate recPrP Sc formation in the absence of RNA. PE facilitated the propagation of PrP Sc molecules derived from all four different animal species tested including mouse, suggesting that unlike RNA, PE is a promiscuous cofactor for PrP Sc formation in vitro. Phospholipase treatment abolished the ability of brain homogenate to reconstitute the propagation of both mouse and hamster PrP Sc molecules. Our results identify a single endogenous cofactor able to facilitate the formation of prions from multiple species in the absence of nucleic acids or other polyanions.PrP | scrapie P rions are mechanistically unique infectious agents that contain a misfolded, membrane-bound, glycoprotein (PrP Sc ) formed by the conformational change of a host-encoded conformer (PrP C ) (1). Conversion of PrP C into PrP Sc is the central event in the formation of infectious prions, but the molecular mechanism underlying conformational change remains poorly understood. In particular, the number and identity of endogenous factors other than PrP required for prion formation has not been determined (2).Cell culture and biochemical studies have implicated several classes of macromolecules such as GAGs, nucleic acids, proteins, and lipids as potential cofactors for prion formation (3). Reconstitution experiments with defined substrates (in which purified PrP molecules are mixed with Prnp 0/0 brain homogenate or purified cofactors that facilitate its conversion to PrP Sc ) have suggested that the conversion mechanism may be relatively simple, requiring only a few components (4, 5). Wild-type hamster prions possessing specific infectivity levels similar to those associated with natural scrapie have been formed de novo by using a defined mixture of purified native PrP C , copurified lipid, and RNA molecules (4), and infectious prions have also been formed de novo from bacterially expressed, recombinant PrP substrate in a reaction facilitated by synthetic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and RNA molecules (5, 6). In summary, infectious prions have not yet been produced either with a single cofactor or in the abs...

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Section: Discussionmentioning

confidence: 99%

Isolation of phosphatidylethanolamine as a solitary cofactor for prion formation in the absence of nucleic acids

Deleault

Piro²,

Walsh³

et al. 2012

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

210

236

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“…Until the late 1970s it was a common practice in UK to additionally subject greaves to a solvent extraction process involving the exposure to hot solvents such as benzene, hexane, heptane, and others, followed by dry heat and/or steam heat at a temperature of 100 7C, before producing meat and bone meal. Although the abandonment of this solvent extraction process by the British rendering industry appeared not to be the key factor for the emergence of BSE [10], it emphasised the importance of suitable decontamination methods. It is known that the efficiency of heat inactivation of conventional microorganisms is impaired by the presence of fat [11,12].…”

Section: Introductionmentioning

confidence: 99%

“…Following Western blot-derived degradation data, the heat stability of PrP27-30 is also raised by the presence of lipids [13], which is of particular importance as the fat content of mammalian tissues and particularly of brain is considerably high. Thus, rendering procedures are of particular concern for spreading the disease [8,10,14]. We will not review rendering procedures in the past concerning the BSE risk.…”

Section: Introductionmentioning

confidence: 99%

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Thermal degradation of prions in the presence of fats: Implication for oleochemical processes

Müller¹,

Riesner²

2005

Eur. J. Lipid Sci. Technol.

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Bovine tallow is widely used as raw material for oleochemical processes, i.e. the manufacturing of fatty acids and glycerol and their derivatives. The basic oleochemical process, i.e. the hydrolytic fat splitting under industrial conditions of 200-260 7C at corresponding pressure and a minimum residence time of 20 min, is considered to guarantee the safety of all tallow-derived products. As to the present day no experimental data on the safety of fatty acids and glycerol in case of a hypothetical contamination of tallow with TSE agents under technically relevant conditions are available, the intention of this study was to provide quantitative data for the destruction of prions. This short communication reports the first part of a research project simulating prion inactivation under manufacturing conditions of the upper part of industrial fatsplitting columns (fatty acid regime) on a laboratory scale. To establish worst-case destruction factors, the degradation of prion protein was analysed in dependence upon temperature. The industrial process conditions of the fatty acid regime of hydrolytic fat splitting provide an additional safety factor of at least 1610 7 , confirming that all fatty acids can be regarded as safe, irrespective of their origin.

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“…However, evidence suggests that instruments not precleaned before sterilizing may still harAdult ID Notes bour the CJD agent in the centre of the tissues or fluid remaining on the instruments (9). It is believed that the sterilization process may seal the outer layer of the tissues that remains on the instruments, which consequently protects the CJD agent in the core of these particles (36). Furthermore, studies that evaluate the efficacy of a combination of cleaning and sterilization in the clinical setting have not been published (4).…”

Section: Infection Control Issues and Cjdmentioning

confidence: 99%

Creutzfeldt‐Jakob Disease and Infection Control

Johnston

Conly

2001

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Over the past year, several situations have occurred in Canada in which patients who had recently undergone a surgical procedure were subsequently diagnosed with confirmed or suspected Creutzfeldt-Jakob disease (CJD). This raised concerns over contamination of surgical instruments: which instruments might have been contaminated from direct exposure to tissues; can instruments become cross-contaminated by exposure to other contaminated instruments; what assessment is necessary to determine cross-contamination; and what should be done with instruments that have been contaminated. Additionally, should there be a patient traceback in the face of potential but unproven exposure? Unfortunately, there are no easy answers to most of the above questions. Australia, the United Kingdom and the World Health Organization have developed guidelines for the infection control management of patients with CJD, as well as instruments and devices that come into contact with them and their tissues (1-3). Health Canada's draft CJD infection control guidelines, withdrawn from the Health Canada Web site until safety concerns regarding sodium hydroxide can be addressed, closely mirrored recommendations made in those documents. The Centers for Disease Control and Prevention guidelines for CJD are under revision. However, a recent American publication made recommendations on what procedures should be used for reprocessing items that have been in contact with the prion protein (PrP) (4). These recommendations differ substantially from the draft Canadian guidelines. This article reviews current knowledge about CJD, and highlights some of the infection control concerns and controversies.

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Solvent extraction as an adjunct to rendering: the effect on BSE and scrapie agents of hot solvents followed by dry heat and steam

Cited by 29 publications

References 17 publications

Isolation of phosphatidylethanolamine as a solitary cofactor for prion formation in the absence of nucleic acids

Isolation of phosphatidylethanolamine as a solitary cofactor for prion formation in the absence of nucleic acids

Thermal degradation of prions in the presence of fats: Implication for oleochemical processes

Creutzfeldt‐Jakob Disease and Infection Control

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