@article{78fe595023e644618225b3897743fbda,
title = "Subclinical infection occurs frequently following low dose exposure to prions by blood transfusion",
abstract = "Infectious prion diseases have very long incubation periods, and the role that subclinical infections play in transmission, persistence and re-emergence of these diseases is unclear. In this study, we used a well-established model of vCJD (sheep experimentally infected with bovine spongiform encephalopathy, BSE) to determine the prevalence of subclinical infection following exposure by blood transfusion from infected donors. Many recipient sheep survived for years post-transfusion with no clinical signs and no disease-associated PrP (PrPSc) found in post mortem tissue samples by conventional tests. Using a sensitive protein misfolding cyclic amplification assay (PMCA), we found that the majority of these sheep had detectable PrPSc in lymph node samples, at levels approximately 105-106 times lower than in equivalent samples from clinically positive sheep. Further testing revealed the presence of PrPSc in other tissues, including brain, but not in blood samples. The results demonstrate that subclinical infection is a frequent outcome of low dose prion infection by a clinically relevant route for humans (blood transfusion). The long term persistence of low levels of infection has important implications for prion disease control and the risks of re-emergent infections in both humans and animals.",
keywords = "Animals, Asymptomatic Infections, Blood Transfusion, Cattle, Encephalopathy, Bovine Spongiform, PrPSc Proteins/metabolism, Prions, Sheep",
author = "Khalid Salamat and Paula Stewart and Helen Brown and Kyle Tan and Allister Smith and {De Wolf}, Christopher and Richard Alejo-Blanco and Turner, {Marc L} and Manson, {Jean C.} and Sandra McCutcheon and Fiona Houston",
note = "Funding Information: The authors thank past and present members of large animal research services at the Institute for Animal Health, Compton and the Roslin Institute for excellent care of the sheep and technical assistance with experimental procedures. We are grateful for the generous provision of TgShpXI transgenic mouse brains for use as PMCA substrate by Olivier Andreoletti (INRAE-ENVT, Toulouse, France). We acknowledge the contribution of Hugh Simmons and colleagues from the Animal and Plant Health Agency (APHA) and ADAS in breeding and provision of sheep for the experiment. We would also like to thank Wilfred Goldmann for advice and support with PRNP genotype analysis, Dawn Drummond and colleagues at Easter Bush pathology for processing tissues for histopathology, and colleagues at SNBTS for preparation and provision of blood bags. The BSE-infected and normal cattle brain homogenates were provided by the Biological Archive Group (formerly TSE Archive) at APHA Weybridge. The results presented in the paper are based on independent research commissioned and funded by the Policy Research Programme of the Department of Health and Social Care (“The Effect of Leucodepletion on Transmission of BSE by Transfusion of Sheep Blood Components”; reference 007/0162). The views expressed in the publication are those of the authors and not necessarily those of the Department of Health and Social Care, {\textquoteleft}arms{\textquoteright} length bodies or other government departments. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41598-022-15105-w",
language = "English",
volume = "12",
pages = "1--11",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}