Second passage experiments of chronic wasting disease in transgenic mice overexpressing human prion protein
Abstract Chronic wasting disease (CWD) is a prion disease of cervids including deer, elk, reindeer, and moose. Human consumption of cervids is common, therefore assessing the risk potential of CWD transmission to humans is critical. In a previous study, we tested CWD transmission via intracerebral i...
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Veterinary Research |
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| Online Access: | https://doi.org/10.1186/s13567-022-01130-0 |
| _version_ | 1811198463365349376 |
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| author | Brent Race Chase Baune Katie Williams James F. Striebel Andrew G. Hughson Bruce Chesebro |
| author_facet | Brent Race Chase Baune Katie Williams James F. Striebel Andrew G. Hughson Bruce Chesebro |
| author_sort | Brent Race |
| collection | DOAJ |
| description | Abstract Chronic wasting disease (CWD) is a prion disease of cervids including deer, elk, reindeer, and moose. Human consumption of cervids is common, therefore assessing the risk potential of CWD transmission to humans is critical. In a previous study, we tested CWD transmission via intracerebral inoculation into transgenic mice (tg66 and tgRM) that over-expressed human prion protein. Mice screened by traditional prion detection assays were negative. However, in a group of 88 mice screened by the ultrasensitive RT-QuIC assay, we identified 4 tg66 mice that produced inconsistent positive RT-QuIC reactions. These data could be false positive reactions, residual input inoculum or indicative of subclinical infections suggestive of cross species transmission of CWD to humans. Additional experiments were required to understand the nature of the prion seeding activity in this model. In this manuscript, second passage experiments using brains from mice with weak prion seeding activity showed they were not infectious to additional recipient tg66 mice. Clearance experiments showed that input CWD prion seeding activity was eliminated by 180 days in tg66 mice and PrPKO mice, which are unable to replicate prion protein, indicating that the weak positive levels of seeding activity detected at later time points was not likely residual inoculum. The failure of CWD prions to cause disease in tg66 after two sequential passages suggested that a strong species barrier prevented CWD infection of mice expressing human prion protein. |
| first_indexed | 2024-04-12T01:32:12Z |
| format | Article |
| id | doaj.art-b984f435e5da496dbfd4f1678c8d4255 |
| institution | Directory Open Access Journal |
| issn | 1297-9716 |
| language | English |
| last_indexed | 2024-04-12T01:32:12Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj.art-b984f435e5da496dbfd4f1678c8d42552022-12-22T03:53:27ZengBMCVeterinary Research1297-97162022-12-015311910.1186/s13567-022-01130-0Second passage experiments of chronic wasting disease in transgenic mice overexpressing human prion proteinBrent Race0Chase Baune1Katie Williams2James F. Striebel3Andrew G. Hughson4Bruce Chesebro5Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of HealthAbstract Chronic wasting disease (CWD) is a prion disease of cervids including deer, elk, reindeer, and moose. Human consumption of cervids is common, therefore assessing the risk potential of CWD transmission to humans is critical. In a previous study, we tested CWD transmission via intracerebral inoculation into transgenic mice (tg66 and tgRM) that over-expressed human prion protein. Mice screened by traditional prion detection assays were negative. However, in a group of 88 mice screened by the ultrasensitive RT-QuIC assay, we identified 4 tg66 mice that produced inconsistent positive RT-QuIC reactions. These data could be false positive reactions, residual input inoculum or indicative of subclinical infections suggestive of cross species transmission of CWD to humans. Additional experiments were required to understand the nature of the prion seeding activity in this model. In this manuscript, second passage experiments using brains from mice with weak prion seeding activity showed they were not infectious to additional recipient tg66 mice. Clearance experiments showed that input CWD prion seeding activity was eliminated by 180 days in tg66 mice and PrPKO mice, which are unable to replicate prion protein, indicating that the weak positive levels of seeding activity detected at later time points was not likely residual inoculum. The failure of CWD prions to cause disease in tg66 after two sequential passages suggested that a strong species barrier prevented CWD infection of mice expressing human prion protein.https://doi.org/10.1186/s13567-022-01130-0RT-QuICprioncross-species transmissionbarrierchronic wasting diseasetransgenic mice |
| spellingShingle | Brent Race Chase Baune Katie Williams James F. Striebel Andrew G. Hughson Bruce Chesebro Second passage experiments of chronic wasting disease in transgenic mice overexpressing human prion protein Veterinary Research RT-QuIC prion cross-species transmission barrier chronic wasting disease transgenic mice |
| title | Second passage experiments of chronic wasting disease in transgenic mice overexpressing human prion protein |
| title_full | Second passage experiments of chronic wasting disease in transgenic mice overexpressing human prion protein |
| title_fullStr | Second passage experiments of chronic wasting disease in transgenic mice overexpressing human prion protein |
| title_full_unstemmed | Second passage experiments of chronic wasting disease in transgenic mice overexpressing human prion protein |
| title_short | Second passage experiments of chronic wasting disease in transgenic mice overexpressing human prion protein |
| title_sort | second passage experiments of chronic wasting disease in transgenic mice overexpressing human prion protein |
| topic | RT-QuIC prion cross-species transmission barrier chronic wasting disease transgenic mice |
| url | https://doi.org/10.1186/s13567-022-01130-0 |
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