Short incubation periods of atypical H-type BSE in cattle with EK211 and KK211 prion protein genotypes after intracranial inoculation

Eric D Cassmann; Alexis J Frese; Kelsey A Becker; Justin J Greenlee

doi:10.3389/fvets.2023.1301998

Short incubation periods of atypical H-type BSE in cattle with EK211 and KK211 prion protein genotypes after intracranial inoculation

Front Vet Sci. 2023 Nov 3:10:1301998. doi: 10.3389/fvets.2023.1301998. eCollection 2023.

Authors

Eric D Cassmann¹, Alexis J Frese^{1

2

3}, Kelsey A Becker^{1

2}, Justin J Greenlee¹

Affiliations

¹ Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, IA, United States.
² Oak Ridge Institute for Science and Education, Oak Ridge, TN, United States.
³ Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.

Abstract

In 2006, a case of atypical H-type BSE (H-BSE) was found to be associated with a germline mutation in the PRNP gene that resulted in a lysine substitution for glutamic acid at codon 211 (E211K). The E211K amino acid substitution in cattle is analogous to E200K in humans, which is associated with the development of genetic Creutzfeldt-Jakob disease (CJD). In the present study, we aimed to determine the effect of the EK211 prion protein genotype on incubation time in cattle inoculated with the agent of H-BSE; to characterize the molecular profile of H-BSE in KK211 and EK211 genotype cattle; and to assess the influence of serial passage on BSE strain. Eight cattle, representing three PRNP genotype groups (EE211, EK211, and KK211), were intracranially inoculated with the agent of H-BSE originating from either a case in a cow with the EE211 prion protein genotype or a case in a cow with E211K amino acid substitution. All inoculated animals developed clinical disease; post-mortem samples were collected, and prion disease was confirmed through enzyme immunoassay, anti-PrP^Sc immunohistochemistry, and western blot. Western blot molecular analysis revealed distinct patterns in a steer with KK211 H-BSE compared to EK211 and EE211 cattle. Incubation periods were significantly shorter in cattle with the EK211 and KK211 genotypes compared to the EE211 genotype. Inoculum type did not significantly influence the incubation period. This study demonstrates a shorter incubation period for H-BSE in cattle with the K211 genotype in both the homozygous and heterozygous forms.

Keywords: E211K; H-BSE; PRNP; atypical BSE; bovine spongiform encephalopathy; prion diseases; prion protein; transmissible spongiform encephalopathy.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agricultural Research Service, Maryland, United States. The funders of the work did not influence the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This research was supported in part by an appointment to the Agricultural Research Service (ARS) Research Participation Program administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and the U.S. Department of Agriculture (USDA). ORISE is managed by ORAU under DOE contract number DE-SC0014664.