Transmission studies of chronic wasting disease to transgenic mice overexpressing human prion protein using the RT-QuIC assay
Abstract Chronic wasting disease (CWD) is a fatal prion disease which infects deer, elk and moose. CWD was first described as a wasting syndrome in captive deer in Colorado and Wyoming wildlife facilities from 1967 to 1979. Currently, CWD has been reported in 26 states of the USA, three Canadian pro...
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | Veterinary Research |
| Online Access: | http://link.springer.com/article/10.1186/s13567-019-0626-2 |
| _version_ | 1828826563960897536 |
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| author | Brent Race Katie Williams Bruce Chesebro |
| author_facet | Brent Race Katie Williams Bruce Chesebro |
| author_sort | Brent Race |
| collection | DOAJ |
| description | Abstract Chronic wasting disease (CWD) is a fatal prion disease which infects deer, elk and moose. CWD was first described as a wasting syndrome in captive deer in Colorado and Wyoming wildlife facilities from 1967 to 1979. Currently, CWD has been reported in 26 states of the USA, three Canadian provinces, South Korea, Norway and Finland. Since human consumption of cervids is common, it is critical to determine if CWD can infect humans. Published research, including epidemiologic studies and transmission studies using animal models, including transgenic mice that express human prion protein, have suggested existence of a strong species barrier between cervid CWD and humans. In the current study, we tested CWD transmission into two additional strains of transgenic mice (tg66 and tgRM). These mice over-express human prion protein at high levels and are highly sensitive to infection by human-tropic prions. One hundred and eight mice were inoculated intracerebrally with three different sources of CWD. After long periods of observation, brain tissues from CWD-inoculated mice were screened for evidence of prion infection by RT-QuIC, immunohistochemistry (IHC) and immunoblot. No IHC or immunoblot evidence was found to suggest transmission had occurred, and most mice were negative by RT-QuIC assay. However, four mice with inconsistent positive RT-QuIC reactions were detected. The seeding activity detected in these mice may represent a low level of CWD agent, suggesting a possible transfer of CWD infection. Alternatively, these results might be due to false positive reactions or residual CWD inoculum. |
| first_indexed | 2024-12-12T14:41:38Z |
| format | Article |
| id | doaj.art-03063eb572e745f1998429f7b5ea5210 |
| institution | Directory Open Access Journal |
| issn | 1297-9716 |
| language | English |
| last_indexed | 2024-12-12T14:41:38Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj.art-03063eb572e745f1998429f7b5ea52102022-12-22T00:21:12ZengBMCVeterinary Research1297-97162019-01-0150111410.1186/s13567-019-0626-2Transmission studies of chronic wasting disease to transgenic mice overexpressing human prion protein using the RT-QuIC assayBrent Race0Katie Williams1Bruce Chesebro2Laboratory 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 fatal prion disease which infects deer, elk and moose. CWD was first described as a wasting syndrome in captive deer in Colorado and Wyoming wildlife facilities from 1967 to 1979. Currently, CWD has been reported in 26 states of the USA, three Canadian provinces, South Korea, Norway and Finland. Since human consumption of cervids is common, it is critical to determine if CWD can infect humans. Published research, including epidemiologic studies and transmission studies using animal models, including transgenic mice that express human prion protein, have suggested existence of a strong species barrier between cervid CWD and humans. In the current study, we tested CWD transmission into two additional strains of transgenic mice (tg66 and tgRM). These mice over-express human prion protein at high levels and are highly sensitive to infection by human-tropic prions. One hundred and eight mice were inoculated intracerebrally with three different sources of CWD. After long periods of observation, brain tissues from CWD-inoculated mice were screened for evidence of prion infection by RT-QuIC, immunohistochemistry (IHC) and immunoblot. No IHC or immunoblot evidence was found to suggest transmission had occurred, and most mice were negative by RT-QuIC assay. However, four mice with inconsistent positive RT-QuIC reactions were detected. The seeding activity detected in these mice may represent a low level of CWD agent, suggesting a possible transfer of CWD infection. Alternatively, these results might be due to false positive reactions or residual CWD inoculum.http://link.springer.com/article/10.1186/s13567-019-0626-2 |
| spellingShingle | Brent Race Katie Williams Bruce Chesebro Transmission studies of chronic wasting disease to transgenic mice overexpressing human prion protein using the RT-QuIC assay Veterinary Research |
| title | Transmission studies of chronic wasting disease to transgenic mice overexpressing human prion protein using the RT-QuIC assay |
| title_full | Transmission studies of chronic wasting disease to transgenic mice overexpressing human prion protein using the RT-QuIC assay |
| title_fullStr | Transmission studies of chronic wasting disease to transgenic mice overexpressing human prion protein using the RT-QuIC assay |
| title_full_unstemmed | Transmission studies of chronic wasting disease to transgenic mice overexpressing human prion protein using the RT-QuIC assay |
| title_short | Transmission studies of chronic wasting disease to transgenic mice overexpressing human prion protein using the RT-QuIC assay |
| title_sort | transmission studies of chronic wasting disease to transgenic mice overexpressing human prion protein using the rt quic assay |
| url | http://link.springer.com/article/10.1186/s13567-019-0626-2 |
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