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ARS Home Midwest Area Ames, Iowa National Animal Disease Center Virus and Prion Research Research





- Greenlee, Justin
- Animal Health (103)

Research Project: **Location:
                            Virus and Prion Research** Project Number: 5030-32000-228-019-S
                        
                        Project Type: Non-Assistance Cooperative Agreement Start Date: Sep 1, 2022
                        
                        End Date: Aug 31, 2024 **Objective:**
                        
                        The objective of this agreement is to develop a model that can experimentally generate CWD- and atypical BSE-derived abnormal prion protein (PrPSc) using the human prion protein. The model will be used to: 1) explore the mechanism of CWD and atypical BSE prion-seeded conversion of human prion protein, and 2) identify molecular biomarkers for monitoring and probing potential emergence of CWD- and atypical BSE-derived cases of human prion disease. **Approach:**
                        
                        A combination of an in vitro amplification method (protein misfolding cyclic amplification; PMCA) and in vivo animal bioassays will be used to investigate the molecular events of CWD- and atypical BSE-induced conversion of human brain PrPC into PrPSc and to develop molecular biomarkers for monitoring and probing potential CWD- and atypical BSE-derived human prion diseases. Seed from approximately 20 CWD isolates will be used in PMCA assays to assess the role of human codon 129 polymorphisms on prion conversion. PMCA generated seeds from atypical H and L-type BSE cases will be compared to classical cases to compare potential transmission aspects of BSE isolates. All PMCE-induced CWD and BSE transmissions to human prion protein will be bioassayed in mouse models to compare neuropathologic features to those of known phenotypes of human Creutzfeldt-Jakob disease.


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