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

## TL;DR

The study found no evidence of subclinical prion infection in sheep that were orally exposed to BSE, suggesting the oral route is less effective than blood transfusion for causing silent infections.

## Contribution

The study provides new evidence that oral exposure to prions is less likely to cause subclinical infection compared to intravenous exposure.

## Key findings

- No PrPSc was detected in lymph node/tonsil tissues of 15 orally challenged sheep.
- A wider range of tissues from 5 sheep also showed no signs of PrPSc.
- Oral exposure appears less efficient than blood transfusion for establishing subclinical prion infection.

## 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 (PrPSc; 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 PrPSc 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.