Modulation of innate immune response to viruses including SARS-CoV-2 by progesterone
Abstract Whether and how innate antiviral response is regulated by humoral metabolism remains enigmatic. We show that viral infection induces progesterone via the hypothalamic-pituitary-adrenal axis in mice. Progesterone induces downstream antiviral genes and promotes innate antiviral response in ce...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-04-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-022-00981-5 |
| _version_ | 1811289438007853056 |
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| author | Shan Su Duo Hua Jin-Peng Li Xia-Nan Zhang Lei Bai Li-Bo Cao Yi Guo Ming Zhang Jia-Zhen Dong Xiao-Wei Liang Ke Lan Ming-Ming Hu Hong-Bing Shu |
| author_facet | Shan Su Duo Hua Jin-Peng Li Xia-Nan Zhang Lei Bai Li-Bo Cao Yi Guo Ming Zhang Jia-Zhen Dong Xiao-Wei Liang Ke Lan Ming-Ming Hu Hong-Bing Shu |
| author_sort | Shan Su |
| collection | DOAJ |
| description | Abstract Whether and how innate antiviral response is regulated by humoral metabolism remains enigmatic. We show that viral infection induces progesterone via the hypothalamic-pituitary-adrenal axis in mice. Progesterone induces downstream antiviral genes and promotes innate antiviral response in cells and mice, whereas knockout of the progesterone receptor PGR has opposite effects. Mechanistically, stimulation of PGR by progesterone activates the tyrosine kinase SRC, which phosphorylates the transcriptional factor IRF3 at Y107, leading to its activation and induction of antiviral genes. SARS-CoV-2-infected patients have increased progesterone levels, and which are co-related with decreased severity of COVID-19. Our findings reveal how progesterone modulates host innate antiviral response, and point to progesterone as a potential immunomodulatory reagent for infectious and inflammatory diseases. |
| first_indexed | 2024-04-13T03:54:49Z |
| format | Article |
| id | doaj.art-a7a982087ef54da1a75415abf94a99d1 |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-04-13T03:54:49Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-a7a982087ef54da1a75415abf94a99d12022-12-22T03:03:40ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352022-04-017111410.1038/s41392-022-00981-5Modulation of innate immune response to viruses including SARS-CoV-2 by progesteroneShan Su0Duo Hua1Jin-Peng Li2Xia-Nan Zhang3Lei Bai4Li-Bo Cao5Yi Guo6Ming Zhang7Jia-Zhen Dong8Xiao-Wei Liang9Ke Lan10Ming-Ming Hu11Hong-Bing Shu12Department of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan UniversityDepartment of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan UniversityDepartment of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan UniversityState Key Laboratory of Virology, College of Life Sciences, Wuhan UniversityState Key Laboratory of Virology, College of Life Sciences, Wuhan UniversityDepartment of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan UniversityState Key Laboratory of Virology, College of Life Sciences, Wuhan UniversityDepartment of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan UniversityState Key Laboratory of Virology, College of Life Sciences, Wuhan UniversityState Key Laboratory of Virology, College of Life Sciences, Wuhan UniversityDepartment of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan UniversityDepartment of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan UniversityDepartment of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan UniversityAbstract Whether and how innate antiviral response is regulated by humoral metabolism remains enigmatic. We show that viral infection induces progesterone via the hypothalamic-pituitary-adrenal axis in mice. Progesterone induces downstream antiviral genes and promotes innate antiviral response in cells and mice, whereas knockout of the progesterone receptor PGR has opposite effects. Mechanistically, stimulation of PGR by progesterone activates the tyrosine kinase SRC, which phosphorylates the transcriptional factor IRF3 at Y107, leading to its activation and induction of antiviral genes. SARS-CoV-2-infected patients have increased progesterone levels, and which are co-related with decreased severity of COVID-19. Our findings reveal how progesterone modulates host innate antiviral response, and point to progesterone as a potential immunomodulatory reagent for infectious and inflammatory diseases.https://doi.org/10.1038/s41392-022-00981-5 |
| spellingShingle | Shan Su Duo Hua Jin-Peng Li Xia-Nan Zhang Lei Bai Li-Bo Cao Yi Guo Ming Zhang Jia-Zhen Dong Xiao-Wei Liang Ke Lan Ming-Ming Hu Hong-Bing Shu Modulation of innate immune response to viruses including SARS-CoV-2 by progesterone Signal Transduction and Targeted Therapy |
| title | Modulation of innate immune response to viruses including SARS-CoV-2 by progesterone |
| title_full | Modulation of innate immune response to viruses including SARS-CoV-2 by progesterone |
| title_fullStr | Modulation of innate immune response to viruses including SARS-CoV-2 by progesterone |
| title_full_unstemmed | Modulation of innate immune response to viruses including SARS-CoV-2 by progesterone |
| title_short | Modulation of innate immune response to viruses including SARS-CoV-2 by progesterone |
| title_sort | modulation of innate immune response to viruses including sars cov 2 by progesterone |
| url | https://doi.org/10.1038/s41392-022-00981-5 |
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