Abstract
Prion transmission can occur by blood transfusion in human variant Creutzfeldt-Jakob disease and in experimental animal models, including sheep. Screening of blood and its derivatives for the presence of prions became therefore a major public health issue. As infectious titer in blood is reportedly low, highly sensitive and robust methods are required to detect prions in blood and blood derived products. The objectives of this study were to compare different methods - in vitro, ex vivo and in vivo assays - to detect prion infectivity in cells prepared from blood samples obtained from scrapie infected sheep at different time points of the disease. Protein misfolding cyclic amplification (PMCA) and bioassays in transgenic mice expressing the ovine prion protein were the most efficient methods to identify infected animals at any time of the disease (asymptomatic to terminally-ill stages). However scrapie cell and cerebellar organotypic slice culture assays designed to replicate ovine prions in culture also allowed detection of prion infectivity in blood cells from asymptomatic sheep. These findings confirm that white blood cells are appropriate targets for preclinical detection and introduce ex vivo tools to detect blood infectivity during the asymptomatic stage of the disease.
Highlights
IntroductionTransmissible spongiform encephalopathies (TSE) or prion diseases are deadly infectious neurodegenerative diseases naturally affecting a broad range of mammalian species including humans (Creutzfeldt-Jakob disease-CJD), goats, sheep (scrapie), cattle (bovine spongiform encephalopathy-BSE) and cervids (chronic wasting disease-CWD)
Transmissible spongiform encephalopathies (TSE) or prion diseases are deadly infectious neurodegenerative diseases naturally affecting a broad range of mammalian species including humans (Creutzfeldt-Jakob disease-CJD), goats, sheep, cattle and cervids
Four cases of vCJD transmission were reported in individuals that were transfused with blood from asymptomatic donors that subsequently developed vCJD, strongly arguing that human blood can be infectious as well [11,12,13]
Summary
Transmissible spongiform encephalopathies (TSE) or prion diseases are deadly infectious neurodegenerative diseases naturally affecting a broad range of mammalian species including humans (Creutzfeldt-Jakob disease-CJD), goats, sheep (scrapie), cattle (bovine spongiform encephalopathy-BSE) and cervids (chronic wasting disease-CWD). Prions replicate in tissues other than the nervous system, mainly lymphoid tissues It is notably the case for vCJD and eventually the clinical phase could even not appear resulting in an asymptomatic carriage of vCJD infection [2,3]. Four cases of vCJD transmission were reported in individuals that were transfused with blood from asymptomatic donors that subsequently developed vCJD, strongly arguing that human blood can be infectious as well [11,12,13]. Prevention of vCJD transmission by blood transfusion is a major public health issue
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