BSE can propagate in sheep co-infected or pre-infected with scrapie

Abstract To understand the possible role of mixed-prion infections in disease presentation, the current study reports the co-infection of sheep with bovine spongiform encephalopathy (BSE) and scrapie. The bovine BSE agent was inoculated subcutaneously into sheep with ARQ/ARQ or VRQ/ARQ PRNP genotype...

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Autores principales:	Angela Chong, James D. Foster, Wilfred Goldmann, Lorenzo Gonzalez, Martin Jeffrey, Matthew J. O’Connor, Keith Bishop, Ben C. Maddison, E. Fiona Houston, Kevin C. Gough, Nora Hunter
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8389f00c95af4eeab062820d78120c76
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spelling	oai:doaj.org-article:8389f00c95af4eeab062820d78120c762021-12-02T17:52:23ZBSE can propagate in sheep co-infected or pre-infected with scrapie10.1038/s41598-021-91397-82045-2322https://doaj.org/article/8389f00c95af4eeab062820d78120c762021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91397-8https://doaj.org/toc/2045-2322Abstract To understand the possible role of mixed-prion infections in disease presentation, the current study reports the co-infection of sheep with bovine spongiform encephalopathy (BSE) and scrapie. The bovine BSE agent was inoculated subcutaneously into sheep with ARQ/ARQ or VRQ/ARQ PRNP genotypes either at the same time as subcutaneous challenge with scrapie, or three months later. In addition, VRQ/VRQ sheep naturally infected with scrapie after being born into a scrapie-affected flock were challenged subcutaneously with BSE at eight or twenty one months-of-age. Sheep were analysed by incubation period/attack rate, and western blot of brain tissue determined the presence of BSE or scrapie-like PrPSc. Serial protein misfolding cyclic amplification (sPMCA) that can detect very low levels of BSE in the presence of an excess of scrapie agent was also applied to brain and lymphoreticular tissue. For VRQ/ARQ sheep challenged with mixed infections, scrapie-like incubation periods were produced, and no BSE agent was detected. However, whilst ARQ/ARQ sheep developed disease with BSE-like incubation periods, some animals had a dominant scrapie western blot phenotype in brain, but BSE was detected in these sheep by sPMCA. In addition, VRQ/VRQ animals challenged with BSE after natural exposure to scrapie had scrapie-like incubation periods and dominant scrapie PrPSc in brain, but one sheep had BSE detectable by sPMCA in the brain. Overall, the study demonstrates for the first time that for scrapie/BSE mixed infections, VRQ/ARQ sheep with experimental scrapie did not propagate BSE but VRQ/VRQ sheep with natural scrapie could propagate low levels of BSE, and whilst BSE readily propagated in ARQ/ARQ sheep it was not always the dominant PrPSc strain in brain tissue. Indeed, for several animals, a dominant scrapie biochemical phenotype in brain did not preclude the presence of BSE prion.Angela ChongJames D. FosterWilfred GoldmannLorenzo GonzalezMartin JeffreyMatthew J. O’ConnorKeith BishopBen C. MaddisonE. Fiona HoustonKevin C. GoughNora HunterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Angela Chong James D. Foster Wilfred Goldmann Lorenzo Gonzalez Martin Jeffrey Matthew J. O’Connor Keith Bishop Ben C. Maddison E. Fiona Houston Kevin C. Gough Nora Hunter BSE can propagate in sheep co-infected or pre-infected with scrapie
description	Abstract To understand the possible role of mixed-prion infections in disease presentation, the current study reports the co-infection of sheep with bovine spongiform encephalopathy (BSE) and scrapie. The bovine BSE agent was inoculated subcutaneously into sheep with ARQ/ARQ or VRQ/ARQ PRNP genotypes either at the same time as subcutaneous challenge with scrapie, or three months later. In addition, VRQ/VRQ sheep naturally infected with scrapie after being born into a scrapie-affected flock were challenged subcutaneously with BSE at eight or twenty one months-of-age. Sheep were analysed by incubation period/attack rate, and western blot of brain tissue determined the presence of BSE or scrapie-like PrPSc. Serial protein misfolding cyclic amplification (sPMCA) that can detect very low levels of BSE in the presence of an excess of scrapie agent was also applied to brain and lymphoreticular tissue. For VRQ/ARQ sheep challenged with mixed infections, scrapie-like incubation periods were produced, and no BSE agent was detected. However, whilst ARQ/ARQ sheep developed disease with BSE-like incubation periods, some animals had a dominant scrapie western blot phenotype in brain, but BSE was detected in these sheep by sPMCA. In addition, VRQ/VRQ animals challenged with BSE after natural exposure to scrapie had scrapie-like incubation periods and dominant scrapie PrPSc in brain, but one sheep had BSE detectable by sPMCA in the brain. Overall, the study demonstrates for the first time that for scrapie/BSE mixed infections, VRQ/ARQ sheep with experimental scrapie did not propagate BSE but VRQ/VRQ sheep with natural scrapie could propagate low levels of BSE, and whilst BSE readily propagated in ARQ/ARQ sheep it was not always the dominant PrPSc strain in brain tissue. Indeed, for several animals, a dominant scrapie biochemical phenotype in brain did not preclude the presence of BSE prion.
format	article
author	Angela Chong James D. Foster Wilfred Goldmann Lorenzo Gonzalez Martin Jeffrey Matthew J. O’Connor Keith Bishop Ben C. Maddison E. Fiona Houston Kevin C. Gough Nora Hunter
author_facet	Angela Chong James D. Foster Wilfred Goldmann Lorenzo Gonzalez Martin Jeffrey Matthew J. O’Connor Keith Bishop Ben C. Maddison E. Fiona Houston Kevin C. Gough Nora Hunter
author_sort	Angela Chong
title	BSE can propagate in sheep co-infected or pre-infected with scrapie
title_short	BSE can propagate in sheep co-infected or pre-infected with scrapie
title_full	BSE can propagate in sheep co-infected or pre-infected with scrapie
title_fullStr	BSE can propagate in sheep co-infected or pre-infected with scrapie
title_full_unstemmed	BSE can propagate in sheep co-infected or pre-infected with scrapie
title_sort	bse can propagate in sheep co-infected or pre-infected with scrapie
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8389f00c95af4eeab062820d78120c76
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BSE can propagate in sheep co-infected or pre-infected with scrapie

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