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<blockquote data-quote="flounder" data-source="post: 1841303" data-attributes="member: 3519"><p><strong>Cattle with the EK211 </strong><em><strong>PRNP</strong></em><strong> polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation</strong></p><p></p><p>Justin J. Greenleea, Eric D. Cassmanna, S. Jo Moorea,b, and M. Heather West Greenleec</p><p></p><p><strong>Aims</strong>: In 2006, a case of H-type bovine spongiform encephalopathy (H-BSE) was reported in a cow with a previously unreported prion protein polymorphism (E211K). The E211K polymorphism is heritable and homologous to the E200K mutation in humans that is the most frequent <em>PRNP</em>mutation associated with familial Creutzfeldt-Jakob disease. Although the prevalence of the E211K polymorphism is low, cattle carrying the K211 allele develop H-type BSE with a rapid onset after experimental inoculation by the intracranial route. The purpose of this study was to investigate whether the agents of H-type BSE or H-type BSE associated with the E211K polymorphism transmit to wild type cattle or cattle with the K211 allele after oronasal exposure.</p><p></p><p>snip…</p><p></p><p><strong>Results</strong>: Three-out-of-four (75%) calves with the EK211 genotype developed clinical signs of H-BSE including inattentiveness, loss of body condition, weakness, ataxia, and muscle fasciculations and were euthanized. Two of the positive EK211steers received H-BSE US 2004 inoculum (Incubation Period (IP): 59.3 and 72.3 months) while the other positive steer received the E211K H-BSE inoculum (IP: 49.7 months). EIA confirmed that abundant misfolded protein (O.D. 2.57–4.0) in the brainstem, and IHC demonstrated PrPScthroughout the brain. All wild type recipient cattle and a single EK211 steer remained asymptomatic for the duration of the experiment (approximately 7 years post-inoculation) and no abnormal prion protein was detected in these cattle by EIA.</p><p></p><p><strong>Conclusions</strong>: This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. Cattle with the EK211 genotype are oronasally susceptible to small doses of the H-BSE agent from either EK211 or EE211 (wild type) donors. Wild-type EE211 cattle remained asymptomatic for the duration of the experiment with this small dose (0.1 g) of inoculum. These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.</p><p></p><p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9467582/" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9467582/</a></p><p></p><p>Title: Transmission of atypical BSE: a possible origin of Classical BSE in cattle</p><p></p><p>snip…</p><p></p><p>Results: After 6 years of incubation, 3/4 animals (2/2 steers IC challenged with brain from P1 L-BSE oral challenge and 1/2 steer IC challenged with brain from P1 H-BSE oral challenge) developed clinical disease. Analysis of these animals revealed high levels of PrPSc in their brains, having biochemical properties similar to that of PrPSc in C-BSE.</p><p></p><p>Conclusion: These results demonstrate the oral transmission potential of atypical BSE in cattle. Surprisingly, regardless of which atypical type of BSE was used for P1 oral challenge, PrPSc in the P2 animals acquired biochemical characteristics similar to that of PrPSc in C-BSE, suggesting atypical BSE as a possible origin of C-BSE in UK.</p><p></p><p><a href="https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf" target="_blank">https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf</a></p><p><strong></strong></p><p><strong>Title:</strong> Disease phenotype of classical sheep scrapie is changed upon experimental passage through white-tailed deer</p><table style='width: 100%'><tr><td></td><td><div style="text-align: left"></div> </td></tr></table> <table style='width: 100%'><tr><td><div style="text-align: left"><strong>Publication Date:</strong> 12/4/2023<br /> <br /> <strong>DOI:</strong> <a href="https://doi.org/10.1371/journal.ppat.1011815" target="_blank">https://doi.org/10.1371/journal.ppat.1011815<br /> </a><br /> <strong>Interpretive Summary:</strong> snip…<br /> <br /> These results indicate that sheep could be susceptible to the scrapie agent after passage through deer if exposed to the agent in natural or agricultural settings, which could be a confounding factor to the scrapie eradication program. National and state regulatory and wildlife officials should consider this information when developing plans to reduce or eliminate TSEs.<br /> <br /> <strong>Technical Abstract:</strong> Transmissible spongiform encephalopathy (TSE) agents have strain variations that influence disease phenotype and may affect the potential for interspecies transmission. Since deer and sheep may use the same grazing land, it is important to understand the potential transmission of TSEs between these species. The US scrapie isolate (No.13-7) had a 100% attack rate in white-tailed deer after oronasal challenge. The purpose of this study was to determine if sheep are susceptible to oronasal challenge with the scrapie agent from white-tailed deer. Suffolk lambs of various prion protein genotypes were challenged by the oronasal route with a 10% brain homogenate from scrapie-affected white-tailed deer. Sheep were euthanized and necropsied upon development of clinical signs or at the end of the experiment (72 months post-inoculation). Tissues were tested for PrPSc by enzyme immunoassay, western blot, and immunohistochemistry. The first sheep (2/2) to develop clinical signs at approximately 29 months post-inoculation (MPI) had the VRQ/VRQ genotype. One of the two sheep with the ARQ/ARQ genotype also developed clinical signs at 48 MPI. This is in contrast to the original No.13-7 inoculum that has a faster incubation period in sheep with the ARQ/ARQ genotype compared to sheep of the VRQ/VRQ genotype. The shorter incubation period in VRQ/VRQ sheep than ARQ/ARQ sheep after passage through deer indicates a phenotype change. This is important because scrapie infected deer could transmit disease to sheep resulting in new scrapie strain properties. This work raises the concern that scrapie infected deer could serve as a confounding factor to scrapie eradication programs as the scrapie agent from deer is transmissible to sheep by the oronasal route.<br /> <br /> <a href="https://www.ars.usda.gov/research/publications/publication/?seqNo115=405929" target="_blank">https://www.ars.usda.gov/research/publications/publication/?seqNo115=405929</a></div> </td></tr></table></blockquote><p></p>
[QUOTE="flounder, post: 1841303, member: 3519"] [B]Cattle with the EK211 [/B][I][B]PRNP[/B][/I][B] polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation[/B] Justin J. Greenleea, Eric D. Cassmanna, S. Jo Moorea,b, and M. Heather West Greenleec [B]Aims[/B]: In 2006, a case of H-type bovine spongiform encephalopathy (H-BSE) was reported in a cow with a previously unreported prion protein polymorphism (E211K). The E211K polymorphism is heritable and homologous to the E200K mutation in humans that is the most frequent [I]PRNP[/I]mutation associated with familial Creutzfeldt-Jakob disease. Although the prevalence of the E211K polymorphism is low, cattle carrying the K211 allele develop H-type BSE with a rapid onset after experimental inoculation by the intracranial route. The purpose of this study was to investigate whether the agents of H-type BSE or H-type BSE associated with the E211K polymorphism transmit to wild type cattle or cattle with the K211 allele after oronasal exposure. snip… [B]Results[/B]: Three-out-of-four (75%) calves with the EK211 genotype developed clinical signs of H-BSE including inattentiveness, loss of body condition, weakness, ataxia, and muscle fasciculations and were euthanized. Two of the positive EK211steers received H-BSE US 2004 inoculum (Incubation Period (IP): 59.3 and 72.3 months) while the other positive steer received the E211K H-BSE inoculum (IP: 49.7 months). EIA confirmed that abundant misfolded protein (O.D. 2.57–4.0) in the brainstem, and IHC demonstrated PrPScthroughout the brain. All wild type recipient cattle and a single EK211 steer remained asymptomatic for the duration of the experiment (approximately 7 years post-inoculation) and no abnormal prion protein was detected in these cattle by EIA. [B]Conclusions[/B]: This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. Cattle with the EK211 genotype are oronasally susceptible to small doses of the H-BSE agent from either EK211 or EE211 (wild type) donors. Wild-type EE211 cattle remained asymptomatic for the duration of the experiment with this small dose (0.1 g) of inoculum. These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains. [URL]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9467582/[/URL] Title: Transmission of atypical BSE: a possible origin of Classical BSE in cattle snip… Results: After 6 years of incubation, 3/4 animals (2/2 steers IC challenged with brain from P1 L-BSE oral challenge and 1/2 steer IC challenged with brain from P1 H-BSE oral challenge) developed clinical disease. Analysis of these animals revealed high levels of PrPSc in their brains, having biochemical properties similar to that of PrPSc in C-BSE. Conclusion: These results demonstrate the oral transmission potential of atypical BSE in cattle. Surprisingly, regardless of which atypical type of BSE was used for P1 oral challenge, PrPSc in the P2 animals acquired biochemical characteristics similar to that of PrPSc in C-BSE, suggesting atypical BSE as a possible origin of C-BSE in UK. [URL]https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf[/URL] [B] Title:[/B] Disease phenotype of classical sheep scrapie is changed upon experimental passage through white-tailed deer [TABLE] [TR] [TD][/TD] [TD][LEFT][/LEFT][/TD] [/TR] [/TABLE] [TABLE] [TR] [TD][LEFT][B]Publication Date:[/B] 12/4/2023 [B]DOI:[/B] [URL='https://doi.org/10.1371/journal.ppat.1011815']https://doi.org/10.1371/journal.ppat.1011815 [/URL] [B]Interpretive Summary:[/B] snip… These results indicate that sheep could be susceptible to the scrapie agent after passage through deer if exposed to the agent in natural or agricultural settings, which could be a confounding factor to the scrapie eradication program. National and state regulatory and wildlife officials should consider this information when developing plans to reduce or eliminate TSEs. [B]Technical Abstract:[/B] Transmissible spongiform encephalopathy (TSE) agents have strain variations that influence disease phenotype and may affect the potential for interspecies transmission. Since deer and sheep may use the same grazing land, it is important to understand the potential transmission of TSEs between these species. The US scrapie isolate (No.13-7) had a 100% attack rate in white-tailed deer after oronasal challenge. The purpose of this study was to determine if sheep are susceptible to oronasal challenge with the scrapie agent from white-tailed deer. Suffolk lambs of various prion protein genotypes were challenged by the oronasal route with a 10% brain homogenate from scrapie-affected white-tailed deer. Sheep were euthanized and necropsied upon development of clinical signs or at the end of the experiment (72 months post-inoculation). Tissues were tested for PrPSc by enzyme immunoassay, western blot, and immunohistochemistry. The first sheep (2/2) to develop clinical signs at approximately 29 months post-inoculation (MPI) had the VRQ/VRQ genotype. One of the two sheep with the ARQ/ARQ genotype also developed clinical signs at 48 MPI. This is in contrast to the original No.13-7 inoculum that has a faster incubation period in sheep with the ARQ/ARQ genotype compared to sheep of the VRQ/VRQ genotype. The shorter incubation period in VRQ/VRQ sheep than ARQ/ARQ sheep after passage through deer indicates a phenotype change. This is important because scrapie infected deer could transmit disease to sheep resulting in new scrapie strain properties. This work raises the concern that scrapie infected deer could serve as a confounding factor to scrapie eradication programs as the scrapie agent from deer is transmissible to sheep by the oronasal route. [URL]https://www.ars.usda.gov/research/publications/publication/?seqNo115=405929[/URL][/LEFT][/TD] [/TR] [/TABLE] [/QUOTE]
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