Decontamination of prion protein (BSE301V) using a genetically engineered protease

J. Dickinson; H. Murdoch; Michael Dennis; Graham Hall; R. Bott; W. D. Crabb; C. Penet; J. M. Sutton; N. D.H. Raven

doi:10.1016/j.jhin.2008.12.007

Decontamination of prion protein (BSE301V) using a genetically engineered protease

J. Dickinson, H. Murdoch, Michael Dennis, Graham Hall, R. Bott, W. D. Crabb, C. Penet, J. M. Sutton^*, N. D.H. Raven

^*Corresponding author for this work

Research & Development Institute Scientific Leaders

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

Abstract

A previous study has demonstrated the potential of alkaline proteases to inactivate bovine spongiform encephalopathy (BSE301V). Here we explored the use of MC3, a genetically engineered variant of Bacillus lentus subtilisin. MC3 was used to digest BSE301V infectious mouse brain homogenate (iMBH). MC3 eliminated all detectable 6H4-immunoreactive material at pH 10 and 12; however, Proteinase K was only partially effective at pH 12. When bioassayed in VM mice, MC3- and Proteinase K-digested iMBH gave respectively 66.6% and 22.7% survival rates. Using a titration series for disease incubation, this equates to a >7 log reduction in infectivity for MC3 and >6 log reduction for Proteinase K. This study demonstrates the potential for thermostable proteases to be developed as effective inactivation processes for prion agents in healthcare management. Crown

Original language	English
Pages (from-to)	65-70
Number of pages	6
Journal	Journal of Hospital Infection
Volume	72
Issue number	1
DOIs	https://doi.org/10.1016/j.jhin.2008.12.007
Publication status	Published - May 2009

Keywords

Bacillus lentus subtilisin
Bovine spongiform encephalopathy
Inactivation processes
Variant Creutzfeldt-Jakob disease

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jhin.2008.12.007

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title = "Decontamination of prion protein (BSE301V) using a genetically engineered protease",

abstract = "A previous study has demonstrated the potential of alkaline proteases to inactivate bovine spongiform encephalopathy (BSE301V). Here we explored the use of MC3, a genetically engineered variant of Bacillus lentus subtilisin. MC3 was used to digest BSE301V infectious mouse brain homogenate (iMBH). MC3 eliminated all detectable 6H4-immunoreactive material at pH 10 and 12; however, Proteinase K was only partially effective at pH 12. When bioassayed in VM mice, MC3- and Proteinase K-digested iMBH gave respectively 66.6% and 22.7% survival rates. Using a titration series for disease incubation, this equates to a >7 log reduction in infectivity for MC3 and >6 log reduction for Proteinase K. This study demonstrates the potential for thermostable proteases to be developed as effective inactivation processes for prion agents in healthcare management. Crown",

keywords = "Bacillus lentus subtilisin, Bovine spongiform encephalopathy, Inactivation processes, Variant Creutzfeldt-Jakob disease",

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AU - Dickinson, J.

AU - Murdoch, H.

AU - Dennis, Michael

AU - Hall, Graham

AU - Bott, R.

AU - Crabb, W. D.

AU - Penet, C.

AU - Sutton, J. M.

AU - Raven, N. D.H.

PY - 2009/5

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AB - A previous study has demonstrated the potential of alkaline proteases to inactivate bovine spongiform encephalopathy (BSE301V). Here we explored the use of MC3, a genetically engineered variant of Bacillus lentus subtilisin. MC3 was used to digest BSE301V infectious mouse brain homogenate (iMBH). MC3 eliminated all detectable 6H4-immunoreactive material at pH 10 and 12; however, Proteinase K was only partially effective at pH 12. When bioassayed in VM mice, MC3- and Proteinase K-digested iMBH gave respectively 66.6% and 22.7% survival rates. Using a titration series for disease incubation, this equates to a >7 log reduction in infectivity for MC3 and >6 log reduction for Proteinase K. This study demonstrates the potential for thermostable proteases to be developed as effective inactivation processes for prion agents in healthcare management. Crown

KW - Bacillus lentus subtilisin

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Decontamination of prion protein (BSE301V) using a genetically engineered protease

Abstract

Keywords

UN SDGs

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