Location: Virus and Prion ResearchTitle: Cattle with the EK211 PRNP polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation
|MOORE, SARA JO - Oak Ridge Institute For Science And Education (ORISE)|
|WEST GREENLEE, HEATHER - Iowa State University|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 6/24/2022
Publication Date: 9/16/2022
Citation: Greenlee, J.J., Cassmann, E.D., Moore, S., West Greenlee, H.M. 2022. Cattle with the EK211 PRNP polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation. Prion 2022 Conference abstracts: pushing the boundaries. 16(1):150. https://doi.org/10.1080/19336896.2022.2091286.
Technical Abstract: 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 PRNP 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. Wild type (EE211) or heterozygous (EK211) cattle were oronasally inoculated with the H-BSE agent from either the US 2004 case (wild type donor; n=3) or from the US 2006 case with the E211K polymorphism (n=4). Cattle were observed daily throughout the course of the experiment for the development of clinical signs. When signs were noted, animals were euthanized and necropsied. Cattle were confirmed positive for abnormal BSE prions by enzyme immunoassay (EIA; Idexx HerdChek BSE Ag Test), anti-PrP immunohistochemistry (IHC) on brainstem, and microscopic examination for vacuolation. 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 EK211 steers 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 PrPSc throughout the brain. All cattle in the EE211 recipient group remain asymptomatic for the duration of the experiment (approximately 7 years post-inoculation). 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 (0.1g) 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.