Detection of PrPres in peripheral tissue in pigs with clinical disease induced by intracerebral challenge with sheep-passaged bovine spongiform encephalopathy agent

Hedman, Carlos ; Otero, Alicia, Douet, Jean-Yves (Universidad de Zaragoza) ; Lacroux, Caroline ; Lugan, Séverine ; Filali, Hicham ; Corbière, Fabien (Universidad de Zaragoza) ; Aron, Naima ; Badiola, Juan José (Universidad de Zaragoza) ; Andréoletti, Olivier ; Bolea, Rosa. (Universidad de Zaragoza)

Resumen: Bovine spongiform encephalopathy (BSE) can be efficiently transmitted to pigs via intrace- rebral inoculation. A clear link has been established between the consumption of products of bovine origin contaminated with the BSE agent and the development of variant Creutz- feldt-Jakob disease in humans. Small ruminants can also naturally develop BSE, and sheep-adapted BSE (Sh-BSE) propagates more efficiently than cattle BSE in pigs and in mouse models expressing porcine prion protein. In addition, Sh-BSE shows greater effi- ciency of transmission to human models than original cow BSE. While infectivity and/or abnormal PrP accumulation have been reported in the central nervous system in BSE- infected pigs, the ability of the agent to replicate in peripheral tissues has not been fully investigated. We previously characterized the presence of prions in a panel of tissues col- lected at the clinical stage of disease from pigs experimentally infected with Sh-BSE. West- ern blot revealed low levels of PrPres accumulation in lymphoid tissues, nerves, and skeletal muscles from 4 of the 5 animals analysed. Using protein misfolding cyclic amplification (PMCA), which we found to be 6 log fold more sensitive than direct WB for the detection of pig BSE, we confirmed the presence of the Sh-BSE agent in lymphoid organs, nerves, ileum, and striated muscles from all 5 inoculated pigs. Surprisingly, PrPres positivity was also detected in white blood cells from one pig using this method. The presence of infectivity in lymphoid tissues, striated muscles, and peripheral nerves was confirmed by bioassay in bovine PrP transgenic mice. These results demonstrate the ability of BSE-derived agents to replicate efficiently in various peripheral tissues in pigs. Although no prion transmission has been reported in pigs following oral BSE challenge, our data support the continuation of the Feed Ban measure implemented to prevent entry of the BSE agent into the feed chain.

Idioma: Inglés

DOI: 10.1371/journal.pone.0199914

Año: 2018

Publicado en: PloS one 13, 7 (2018), 0199914 [14 pp]
ISSN: 1932-6203

Factor impacto JCR: 2.776 (2018)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 23 / 69 = 0.333 (2018) - Q2 - T2

Factor impacto SCIMAGO: 1.1 - Agricultural and Biological Sciences (miscellaneous) (Q1) - Medicine (miscellaneous) (Q1) - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/EUR/INTERREG-POCTEFA/EFA-148-16 REDPRION
Financiación: info:eu-repo/grantAgreement/EUR/INTERREG-POCTEFA/EFA 282-13-TRANSPRION

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)