Susceptibility of Young Sheep to Oral Infection with Bovine Spongiform Encephalopathy Decreases Significantly after Weaning

Abstract

bBovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) (or prion disease) that is readily transmissible to sheep by experimental infection and has the shortest incubation period in animals with the ARQ/ARQ PRNP genotype (at codons 136, 154, and 171). Because it is possible that sheep in the United Kingdom could have been infected with BSE by being fed contaminated meat and bone meal supplements at the same time as cattle, there is considerable interest in the responses of sheep to BSE inoculation. Epidemiological evidence suggests that very young individuals are more susceptible to TSE infection; however, this has never been properly tested in sheep. In the present study, low doses of BSE were fed to lambs of a range of ages (ϳ24 h, 2 to 3 weeks, 3 months, and 6 months) and adult sheep. The incidence of clinical BSE disease after inoculation was high in unweaned lambs (ϳ24 h and 2 to 3 weeks old) but much lower in older weaned animals The incubation period was also found to be influenced by the genotype at codon 141 of the PRNP gene, as lambs that were LF heterozygotes had a longer mean incubation period than those that were homozygotes of either type. The results suggest that sheep in the United Kingdom would have been at high risk of BSE infection only if neonatal animals had inadvertently ingested contaminated supplementary foodstuffs.T ransmissible spongiform encephalopathies (TSEs) are prion diseases that affect many mammals and are associated with the presence of the protein PrP Sc , a protease-resistant form of a normal host protein, PrP C . PrP Sc is believed to form all or part of the infectious agent (44). The natural sheep TSE is scrapie; however, sheep can also be experimentally infected with bovine spongiform encephalopathy (BSE) by several routes, including intracerebral, oral (17), and intravenous (28). The manifestation of clinical signs of BSE following inoculation depends upon a number of factors, the most important being the PRNP genotype. In the Neuropathogenesis Unit, Edinburgh, United Kingdom (NPU), Cheviot sheep, animals homozygous for the ARQ PRNP gene allele (codons 136, 154, and 171 indicated in order) are most susceptible (23). However, for reasons that are currently unknown, a various number of adult ARQ/ARQ sheep will survive a challenge with BSE (16). Understanding this aspect of resistance is of fundamental importance. One potential influence on disease outcome following infection with any TSE is the age at which the individual is challenged. Because of the etiology of scrapie, which suggests that in sheep the risk for infection is very high during the perinatal period, many sheep challenge studies, including the study described in reference 3, have used young lambs rather than adult sheep as infection models. In addition, epidemiological studies in cattle (15) have suggested that in general, younger individuals are more susceptible to infection with BSE, and studies in human beings have shown that more individuals at relatively young ages have b...

Bovine Spongiform Encephalopathy – A Review from the Perspective of Food Safety

“…Sheep were more susceptible to orally inoculated C-BSE brain at their ages less than 12 hr or at 2-3 months than at their ages of 3, 6, and 15-27 months 55) . In sheep, ileal PP (IPP) begins to involute from about 12 weeks old and only a few PP follicles remain in the ileum at 18 months old 56) .…”

Does the Presence of Scrapie Affect the Ability of Current Statutory Discriminatory Tests To Detect the Presence of Bovine Spongiform Encephalopathy?

“…Additional unknowns, if trying to use an in vivo challenge model to recreate possible coinfection, are the age of the animal at challenge, the order in which the challenges occur, and possibly the length of time between the challenges (36)(37)(38).…”

Estimating the impact on food and edible materials of changing scrapie control measures: The scrapie control model

“…Experimental infection of classical BSE in sheep has been well documented (Andreoletti et al, 2006;Jeffrey et al, 2001Jeffrey et al, , 2015Foster et al, 1993Foster et al, , 2001Houston et al, 2015;Tan et al, 2012;McGovern et al, 2015McGovern et al, , 2016van Keulen et al, 2008;Hunter et al, 2012). The sheep PRNP genotype has been found to influence both localisation of PrP d deposition and incubation rate.…”