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Journal of General Virology header logo Journal of General Virology

Volume 106, Issue 3

No evidence of subclinical infection in sheep surviving oral challenge with prions Open Access

Abstract

Variant Creutzfeldt–Jakob disease (vCJD) is a fatal zoonotic disease caused by the ingestion of bovine spongiform encephalopathy (BSE)-infected meat products. Although the number of vCJD cases due to dietary exposure has significantly declined, the true burden of subclinical infections remains uncertain. Several large-scale surveys using appendix tissue samples have indicated the presence of abnormal prion protein (PrP; Sc for scrapie) in lymphoid tissue of a small proportion of the UK population. These may represent silent carriers of infection, with the potential to contribute to transmission, persistence and re-emergence of vCJD. Previously, we showed that subclinical infection is a frequent outcome of low-dose prion exposure by blood transfusion in sheep. To determine whether subclinical infection was also found following low-dose exposure by another clinically relevant route for humans, we screened archived tissues from sheep orally challenged with a range of doses of BSE, which did not show clinical or pathological signs of disease after several years of follow-up post-infection. Using a highly sensitive protein misfolding cyclic amplification assay, we were unable to detect PrP in the lymph node/tonsil of 15 sheep, or in a wider range of lymphoid tissues and brain (medulla oblongata) from a subset of 5 sheep. Our findings suggest that the route of infection/exposure may significantly influence the probability of establishing subclinical infection, with the oral route apparently much less efficient than intravenous infection by blood transfusion in sheep.

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Keyword(s): oral , prion , protein misfolding cyclic amplification (PMCA) , sheep and subclinical
Funding
This study was supported by the:
  • Biotechnology and Biological Sciences Research Council (Award BBS/E/RL/230002C)
    • Principal Award Recipient: NotApplicable
  • Department for Environment, Food and Rural Affairs, UK Government (Award SE1844)
    • Principal Award Recipient: NoraHunter
© 2025 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2025-03-21
2025-12-17

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No evidence of subclinical infection in sheep surviving oral challenge with prions
J. Gen. Virol. 106, 002087 (2025); https://doi.org/10.1099/jgv.0.002087
/content/journal/jgv/10.1099/jgv.0.002087
/content/journal/jgv/10.1099/jgv.0.002087
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