Studies of the transmissibility of the agent of bovine spongiform encephalopathy to pigs

Wells, G. A. H.; Hawkins, S. A. C.; Austin, A. R.; Ryder, Stephen; Done, S.H.; Green, Robert B.; Dexter, Ian; Dawson, M.; Kimberlin, R.H.

doi:10.1099/vir.0.18788-0

Cited by 78 publications

(83 citation statements)

References 38 publications

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“…However, rather than being an indication of a weak species barrier, the permissive spread of BSE to a wide variety of species may reflect the level of BSE contamination in meat and bone meal. Experimentally, it has been possible to infect mice, calves, sheep, goats, and mink via both the parenteral and oral routes, although pigs are only susceptible to the parenteral route of infection (Ryder et al, 2000), with disease failing to occur in pigs monitored for 7 years after oral exposure (Wells et al, 2003). Despite a susceptibility of pigs to infection with BSE, there is no evidence of BSE disease in the domestic pig population, at least using the conventional method of detecting clinical signs confirmed by the histopathological analysis of brain sections or the presence of PrP res .…”

Section: Introductionmentioning

confidence: 99%

Subclinical Bovine Spongiform Encephalopathy Infection in Transgenic Mice Expressing Porcine Prion Protein

Castilla

Gutiérrez‐Adán²,

Brun³

et al. 2004

J. Neurosci.

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The bovine-porcine species barrier to bovine spongiform encephalopathy (BSE) infection was explored by generating transgenic mouse lines expressing the porcine prion protein (PrP) gene. All of the porcine transgenic (poTg) mice showed clinical signs of BSE after intracerebral inoculation with a high-titer BSE inoculum. The protease-resistant PrP (PrP res ) was detected in 14% (3 of 22) of the BSE-infected poTg mice by immunohistochemical or immunoblot analysis. Despite being able to infect 42% (5 of 12) of control mice, a low-dose BSE inoculum failed to penetrate the species barrier in our poTg mouse model. The findings of these infectivity studies suggest that there is a strong species barrier between cows and pigs. However, after second-passage infection of poTg mice using brain homogenates of BSE-inoculated mice scoring negative for the incoming prion protein as inoculum, it was possible to detect the presence of the infectious agent. Thus, porcine-adapted BSE inocula were efficient at infecting poTg mice, giving rise to an incubation period substantially reduced from 300 to 177 d after inoculation and to the presence of PrP res in 100% (21 of 21) of the mice. We were therefore able to conclude that initial exposure to the bovine prion may lead to subclinical infection such that brain homogenates from poTg mice classified as uninfected on the basis of the absence of PrP res are infectious when used to reinoculate poTg mice. Collectively, our findings suggest that these poTg mice could be used as a sensitive bioassay model for prion detection in pigs.

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Section: Introductionmentioning

confidence: 99%

Subclinical Bovine Spongiform Encephalopathy Infection in Transgenic Mice Expressing Porcine Prion Protein

Castilla

Gutiérrez‐Adán²,

Brun³

et al. 2004

J. Neurosci.

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“…The neurohistological changes of BSE bear a high degree of resemblance to those of scrapie, the historical archetype of the transmissible spongiform encephalopathies (Wells et al, 1987). BSE has been transmitted experimentally by parenteral routes from cattle to other cattle (Dawson et al, 1990), to mice (Fraser et al, 1992), to pigs (Wells et al, 2003), and to cynomolgus macaques (Lasmézas et al, 1996). A considerable body of evidence also indicates that BSE has been transmitted, by natural or accidental means, via foodstuffs, to several other animal species and to humans (Kirkwood and Cunningham, 1994;Hill et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Comparative bioinformatics analysis of prion proteins isolated from reptile, rodent, ruminant, and human species

Ahn

Son²

2007

Exp Mol Med

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Prion proteins (PrPs) are infectious pathogens that cause a group of invariably fatal, neurodegenerative diseases, including Creutzfeldt-Jakob disease, by means of an entirely novel mechanism. They are produced by various species, including reptile, rodent, ruminant and mammals, during normal metabolic processes, but they can be slowly changed into pathogenic isoforms upon contact with other infectious PrP isoforms. This transmission can occur across species barriers. In the present study, phylogram for each PrP sequence was generated by PAUP* 4.0 program using Neighbor-Joining method with 1,000 times bootstrapping process for the phylogenetic analysis. The molecular dynamics (MD) simulations were performed by the SANDER module in the AMBER 7 package using Amber 99 force field. All the simulation process was conducted in the IBM p690 Supercomputing System in Korea Institute of Science and Technology Information. To reduce the calculation time, we used 'the Generalized Born (GB) model'. We compared the sequences and structural characteristics of normal and pathogenic (E200K) human PrPs with those of other reptile, rodent, ruminant and mammalian PrPs. Phylogenetic analysis revealed that, although the turtle PrP sequence is the most distinct of the PrPs analyzed, it nonetheless retains five conserved secondary structural elements that are similar to those found in the mammalian PrPs, suggesting that these elements have important functions in vivo. The RMS deviation between the normal and E200K human PrPs was larger than that between the normal human and bovine PrPs, and all of the β-sheet structures in human E200K PrP were very stable during MD simulations.

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“…The agent of BSE transmitted to pigs after multiple-route (concurrent intracranial, intravenous, and intraperitoneal) parenteral inoculation with an incubation period of 17-38 months and resulted in severe neuropil vacuolation and abnormal prion protein (PrP Sc ) accumulation in the brain 3) . Further, infectivity was demonstrated in brain, spinal cord, stomach, small intestine, and pancreas by bioassay in C57BLJ6 mice 22) . However, attempts to transmit BSE to pigs after oral dosing with up to 1.2 kg of brain material from infected cattle was unsuccessful 23) .…”

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confidence: 99%

“…Aged animals inoculated intracranially were detectable by traditional diagnostic methods, however, orally Pigs were exposed to the agent of BSE in contaminated meat and bone meal in many European countries, but no naturally occurring cases have been described and surveys of meat and bone meal fed pigs failed to demonstrate any evidence of TSE 32) . Pigs challenged orally with BSE failed to develop evidence of infection 33) despite observation for up to seven years 22) . These previously published studies along with results of the current study suggest that swine are capable of harboring a prion disease, although epidemiologic evidence is not in support of this occurring under production conditions.…”

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confidence: 99%

Scrapie in Swine: a Diagnostic Challenge

et al. 2016

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A naturally occurring prion disease has not been recognized in swine, but the agent of bovine spongiform encephalopathy does transmit to swine by experimental routes. Swine are thought to have a robust species barrier when exposed to the naturally occurring prion diseases of other species, but the susceptibility of swine to the agent of sheep scrapie has not been thoroughly tested. We conducted this experiment to test the susceptibility of swine to U.S. scrapie isolates by intracranial and oral inoculation. Scrapie inoculum was a pooled 10% (w/v) homogenate derived from the brains of clinically ill sheep from the 4 th passage of a serial passage study of the U.S scrapie agent (No. 13-7) through susceptible sheep (homozygous ARQ at prion protein residues 136, 154, and 171, respectively). Pigs were inoculated intracranially (n=19) with a single 0.75 mL dose or orally (n=24) with 15 mL repeated on 4 consecutive days. Necropsies were done on a subset of animals at approximately six months post inoculation (PI): the time the pigs were expected to reach market weight. Remaining pigs were maintained and monitored for clinical signs of transmissible spongiform encephalopathies (TSE) until study termination at 80 months PI or when removed due to intercurrent disease (primarily lameness). Brain samples were examined by immunohistochemistry (IHC), western blot (WB), enzyme immunoassay (EIA), and for a subset of pigs in each inoculation group, bioassay in mice expressing porcine prion protein. At six-months PI, no evidence of scrapie infection was noted by any diagnostic method. However, at 51 months of incubation or greater, 5 animals were positive by one or more methods: IHC (n=4), WB (n=3), or EIA (n=4). Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie.

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Studies of the transmissibility of the agent of bovine spongiform encephalopathy to pigs

Cited by 78 publications

References 38 publications

Subclinical Bovine Spongiform Encephalopathy Infection in Transgenic Mice Expressing Porcine Prion Protein

Subclinical Bovine Spongiform Encephalopathy Infection in Transgenic Mice Expressing Porcine Prion Protein

Comparative bioinformatics analysis of prion proteins isolated from reptile, rodent, ruminant, and human species

Scrapie in Swine: a Diagnostic Challenge

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