Elimination of olfactory sensory neurons by zinc sulfate inoculation prevents SARS-CoV-2 infection of the brain in K18-hACE2 transgenic mice
Abstract Coronavirus disease-2019 (COVID-19), attributed to the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2), has posed global health challenges since it first emerged in 2019, and its impact continues to persist. The neurotropic nature of SARS-CoV-2 remains undisclosed, thou...
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Nature Portfolio
2024-11-01
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| Online Access: | https://doi.org/10.1038/s41598-024-78538-5 |
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| author | Ji-Hun Lee Eun-Seon Yoo Na-Won Kim Won-Yong Shim Han-Bi Jeong Dong-Hyun Kim Young-Jun Park Sun-Min Seo Jun-Won Yun Jun Won Park Kang-Seuk Choi Ho-Young Lee Jun-Young Seo Ki Taek Nam Je Kyung Seong Yang-Kyu Choi |
| author_facet | Ji-Hun Lee Eun-Seon Yoo Na-Won Kim Won-Yong Shim Han-Bi Jeong Dong-Hyun Kim Young-Jun Park Sun-Min Seo Jun-Won Yun Jun Won Park Kang-Seuk Choi Ho-Young Lee Jun-Young Seo Ki Taek Nam Je Kyung Seong Yang-Kyu Choi |
| author_sort | Ji-Hun Lee |
| collection | DOAJ |
| description | Abstract Coronavirus disease-2019 (COVID-19), attributed to the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2), has posed global health challenges since it first emerged in 2019, and its impact continues to persist. The neurotropic nature of SARS-CoV-2 remains undisclosed, though researchers are proposing hypotheses on how the virus is transmitted to the central nervous system. One of the prevailing hypotheses is that SARS-CoV-2 travels through the olfactory nerve system via the olfactory epithelium (OE). Using a K18-human angiotensin converting-enzyme 2 (hACE2) transgenic mouse model with impaired olfactory sensory neurons (OSNs) induced by zinc sulfate, we examined the role of the olfactory nerve in the brain invasion by SARS-CoV-2. Mice lacking OSNs exhibited reduced levels of viral transmission to the brain, leading to significantly improved outcomes following SARS-CoV-2 infection. Moreover, a positive correlation was observed between viral persistence in the OE and brain infection. These results indicate that early inhibition of the olfactory nerve pathway effectively prevents viral invasion of the brain in K18-hACE2 mice. Our study underscores the significance of the olfactory nerve pathway in the transmission of SARS-CoV-2 to the brain. |
| format | Article |
| id | doaj-art-9b4e8f09ba0b42bebfe4813960748baf |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-9b4e8f09ba0b42bebfe4813960748baf2025-02-09T12:38:16ZengNature PortfolioScientific Reports2045-23222024-11-0114111410.1038/s41598-024-78538-5Elimination of olfactory sensory neurons by zinc sulfate inoculation prevents SARS-CoV-2 infection of the brain in K18-hACE2 transgenic miceJi-Hun Lee0Eun-Seon Yoo1Na-Won Kim2Won-Yong Shim3Han-Bi Jeong4Dong-Hyun Kim5Young-Jun Park6Sun-Min Seo7Jun-Won Yun8Jun Won Park9Kang-Seuk Choi10Ho-Young Lee11Jun-Young Seo12Ki Taek Nam13Je Kyung Seong14Yang-Kyu Choi15Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk UniversityDepartment of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk UniversityDepartment of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk UniversityDepartment of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk UniversityDepartment of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk UniversityDepartment of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk UniversityDepartment of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk UniversityDepartment of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk UniversityLaboratory of Veterinary Toxicology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National UniversityDepartment of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National UniversityLaboratory of Avian Diseases, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National UniversityDepartment of Nuclear Medicine, Seoul National University Bundang HospitalDepartment of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of MedicineDepartment of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of MedicineKorea Model Animal Priority Center, Seoul National UniversityDepartment of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk UniversityAbstract Coronavirus disease-2019 (COVID-19), attributed to the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2), has posed global health challenges since it first emerged in 2019, and its impact continues to persist. The neurotropic nature of SARS-CoV-2 remains undisclosed, though researchers are proposing hypotheses on how the virus is transmitted to the central nervous system. One of the prevailing hypotheses is that SARS-CoV-2 travels through the olfactory nerve system via the olfactory epithelium (OE). Using a K18-human angiotensin converting-enzyme 2 (hACE2) transgenic mouse model with impaired olfactory sensory neurons (OSNs) induced by zinc sulfate, we examined the role of the olfactory nerve in the brain invasion by SARS-CoV-2. Mice lacking OSNs exhibited reduced levels of viral transmission to the brain, leading to significantly improved outcomes following SARS-CoV-2 infection. Moreover, a positive correlation was observed between viral persistence in the OE and brain infection. These results indicate that early inhibition of the olfactory nerve pathway effectively prevents viral invasion of the brain in K18-hACE2 mice. Our study underscores the significance of the olfactory nerve pathway in the transmission of SARS-CoV-2 to the brain.https://doi.org/10.1038/s41598-024-78538-5SARS-CoV-2Olfactory epitheliumOlfactory sensory neuronsBrainZinc sulfateK18-hACE2 |
| spellingShingle | Ji-Hun Lee Eun-Seon Yoo Na-Won Kim Won-Yong Shim Han-Bi Jeong Dong-Hyun Kim Young-Jun Park Sun-Min Seo Jun-Won Yun Jun Won Park Kang-Seuk Choi Ho-Young Lee Jun-Young Seo Ki Taek Nam Je Kyung Seong Yang-Kyu Choi Elimination of olfactory sensory neurons by zinc sulfate inoculation prevents SARS-CoV-2 infection of the brain in K18-hACE2 transgenic mice Scientific Reports SARS-CoV-2 Olfactory epithelium Olfactory sensory neurons Brain Zinc sulfate K18-hACE2 |
| title | Elimination of olfactory sensory neurons by zinc sulfate inoculation prevents SARS-CoV-2 infection of the brain in K18-hACE2 transgenic mice |
| title_full | Elimination of olfactory sensory neurons by zinc sulfate inoculation prevents SARS-CoV-2 infection of the brain in K18-hACE2 transgenic mice |
| title_fullStr | Elimination of olfactory sensory neurons by zinc sulfate inoculation prevents SARS-CoV-2 infection of the brain in K18-hACE2 transgenic mice |
| title_full_unstemmed | Elimination of olfactory sensory neurons by zinc sulfate inoculation prevents SARS-CoV-2 infection of the brain in K18-hACE2 transgenic mice |
| title_short | Elimination of olfactory sensory neurons by zinc sulfate inoculation prevents SARS-CoV-2 infection of the brain in K18-hACE2 transgenic mice |
| title_sort | elimination of olfactory sensory neurons by zinc sulfate inoculation prevents sars cov 2 infection of the brain in k18 hace2 transgenic mice |
| topic | SARS-CoV-2 Olfactory epithelium Olfactory sensory neurons Brain Zinc sulfate K18-hACE2 |
| url | https://doi.org/10.1038/s41598-024-78538-5 |
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