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Conservation of vCJD Strain Properties After Extraction and In Vitro Propagation of PrP(Sc) from Archived Formalin-Fixed Brain and Appendix Tissues Using Highly Sensitive Protein Misfolding Cyclic Amplification

Three retrospective lymphoreticular tissue studies (Appendix I, II, and III) aimed to estimate the UK prevalence of variant Creutzfeldt-Jakob disease (vCJD), following exposure of the population to the bovine spongiform encephalopathy (BSE) agent, in the late 1980s and 1990s. These studies evaluated...

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Autores principales: Suleiman, Suzanne, McGuire, Lynne I., Chong, Angela, Ritchie, Diane L., Boyle, Aileen, McManus, Lee, Brydon, Fraser, Smith, Colin, Knight, Richard, Green, Alison, Diack, Abigail B., Barria, Marcelo A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10533579/
https://www.ncbi.nlm.nih.gov/pubmed/37442858
http://dx.doi.org/10.1007/s12035-023-03444-2
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author Suleiman, Suzanne
McGuire, Lynne I.
Chong, Angela
Ritchie, Diane L.
Boyle, Aileen
McManus, Lee
Brydon, Fraser
Smith, Colin
Knight, Richard
Green, Alison
Diack, Abigail B.
Barria, Marcelo A.
author_facet Suleiman, Suzanne
McGuire, Lynne I.
Chong, Angela
Ritchie, Diane L.
Boyle, Aileen
McManus, Lee
Brydon, Fraser
Smith, Colin
Knight, Richard
Green, Alison
Diack, Abigail B.
Barria, Marcelo A.
author_sort Suleiman, Suzanne
collection PubMed
description Three retrospective lymphoreticular tissue studies (Appendix I, II, and III) aimed to estimate the UK prevalence of variant Creutzfeldt-Jakob disease (vCJD), following exposure of the population to the bovine spongiform encephalopathy (BSE) agent, in the late 1980s and 1990s. These studies evaluated the presence of abnormal prion protein aggregates, in archived formalin-fixed paraffin-embedded (FFPE) appendectomy samples, by immunohistochemical detection. Although there was concordance in the estimated prevalence of vCJD from these studies, the identification of positive specimens from pre- and post-BSE-exposure periods in Appendix III study has raised questions regarding the nature and origin of the detected abnormal prion protein. We applied a robust and novel approach in the extraction of disease-associated prion protein (PrP(Sc)) present in frozen and FFPE samples of brain and appendix from a patient with pathologically confirmed vCJD. The extracted material was used to seed the highly sensitive protein misfolding cyclic amplification assay (hsPMCA) to investigate the in vitro and in vivo propagation properties of the extracted abnormal prion protein. We demonstrate that PrP(Sc) can be successfully extracted from FFPE appendix tissue and propagated in vitro. Bioassay in wild-type and gene-targeted mouse models confirmed that the extracted and amplified product is infectious and retains strain properties consistent with vCJD. This provides a highly sensitive and reliable platform for subsequent analysis of the archived FFPE appendix tissue derived from the Appendix II and III surveys, to further evaluate the nature of the abnormal PrP detected in the positive samples. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-023-03444-2.
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spelling pubmed-105335792023-09-29 Conservation of vCJD Strain Properties After Extraction and In Vitro Propagation of PrP(Sc) from Archived Formalin-Fixed Brain and Appendix Tissues Using Highly Sensitive Protein Misfolding Cyclic Amplification Suleiman, Suzanne McGuire, Lynne I. Chong, Angela Ritchie, Diane L. Boyle, Aileen McManus, Lee Brydon, Fraser Smith, Colin Knight, Richard Green, Alison Diack, Abigail B. Barria, Marcelo A. Mol Neurobiol Article Three retrospective lymphoreticular tissue studies (Appendix I, II, and III) aimed to estimate the UK prevalence of variant Creutzfeldt-Jakob disease (vCJD), following exposure of the population to the bovine spongiform encephalopathy (BSE) agent, in the late 1980s and 1990s. These studies evaluated the presence of abnormal prion protein aggregates, in archived formalin-fixed paraffin-embedded (FFPE) appendectomy samples, by immunohistochemical detection. Although there was concordance in the estimated prevalence of vCJD from these studies, the identification of positive specimens from pre- and post-BSE-exposure periods in Appendix III study has raised questions regarding the nature and origin of the detected abnormal prion protein. We applied a robust and novel approach in the extraction of disease-associated prion protein (PrP(Sc)) present in frozen and FFPE samples of brain and appendix from a patient with pathologically confirmed vCJD. The extracted material was used to seed the highly sensitive protein misfolding cyclic amplification assay (hsPMCA) to investigate the in vitro and in vivo propagation properties of the extracted abnormal prion protein. We demonstrate that PrP(Sc) can be successfully extracted from FFPE appendix tissue and propagated in vitro. Bioassay in wild-type and gene-targeted mouse models confirmed that the extracted and amplified product is infectious and retains strain properties consistent with vCJD. This provides a highly sensitive and reliable platform for subsequent analysis of the archived FFPE appendix tissue derived from the Appendix II and III surveys, to further evaluate the nature of the abnormal PrP detected in the positive samples. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-023-03444-2. Springer US 2023-07-13 2023 /pmc/articles/PMC10533579/ /pubmed/37442858 http://dx.doi.org/10.1007/s12035-023-03444-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Suleiman, Suzanne
McGuire, Lynne I.
Chong, Angela
Ritchie, Diane L.
Boyle, Aileen
McManus, Lee
Brydon, Fraser
Smith, Colin
Knight, Richard
Green, Alison
Diack, Abigail B.
Barria, Marcelo A.
Conservation of vCJD Strain Properties After Extraction and In Vitro Propagation of PrP(Sc) from Archived Formalin-Fixed Brain and Appendix Tissues Using Highly Sensitive Protein Misfolding Cyclic Amplification
title Conservation of vCJD Strain Properties After Extraction and In Vitro Propagation of PrP(Sc) from Archived Formalin-Fixed Brain and Appendix Tissues Using Highly Sensitive Protein Misfolding Cyclic Amplification
title_full Conservation of vCJD Strain Properties After Extraction and In Vitro Propagation of PrP(Sc) from Archived Formalin-Fixed Brain and Appendix Tissues Using Highly Sensitive Protein Misfolding Cyclic Amplification
title_fullStr Conservation of vCJD Strain Properties After Extraction and In Vitro Propagation of PrP(Sc) from Archived Formalin-Fixed Brain and Appendix Tissues Using Highly Sensitive Protein Misfolding Cyclic Amplification
title_full_unstemmed Conservation of vCJD Strain Properties After Extraction and In Vitro Propagation of PrP(Sc) from Archived Formalin-Fixed Brain and Appendix Tissues Using Highly Sensitive Protein Misfolding Cyclic Amplification
title_short Conservation of vCJD Strain Properties After Extraction and In Vitro Propagation of PrP(Sc) from Archived Formalin-Fixed Brain and Appendix Tissues Using Highly Sensitive Protein Misfolding Cyclic Amplification
title_sort conservation of vcjd strain properties after extraction and in vitro propagation of prp(sc) from archived formalin-fixed brain and appendix tissues using highly sensitive protein misfolding cyclic amplification
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10533579/
https://www.ncbi.nlm.nih.gov/pubmed/37442858
http://dx.doi.org/10.1007/s12035-023-03444-2
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