African swine fever virus QP383R dampens type I interferon production by promoting cGAS palmitoylation
Cyclic GMP-AMP synthase (cGAS) recognizes viral DNA and synthesizes cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING/MITA) and downstream mediators to elicit an innate immune response. African swine fever virus (ASFV) proteins can antagonize host immune responses to prom...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1186916/full |
| _version_ | 1827951678774575104 |
|---|---|
| author | Siyuan Hao Siyuan Hao Siyuan Hao Siyuan Hao Xiaojie Zheng Xiaojie Zheng Xiaojie Zheng Xiaojie Zheng Yingqi Zhu Yingqi Zhu Yingqi Zhu Yingqi Zhu Yao Yao Yao Yao Yao Yao Yao Yao Sihan Li Sihan Li Sihan Li Sihan Li Yangyang Xu Yangyang Xu Yangyang Xu Yangyang Xu Wen-hai Feng Wen-hai Feng Wen-hai Feng Wen-hai Feng |
| author_facet | Siyuan Hao Siyuan Hao Siyuan Hao Siyuan Hao Xiaojie Zheng Xiaojie Zheng Xiaojie Zheng Xiaojie Zheng Yingqi Zhu Yingqi Zhu Yingqi Zhu Yingqi Zhu Yao Yao Yao Yao Yao Yao Yao Yao Sihan Li Sihan Li Sihan Li Sihan Li Yangyang Xu Yangyang Xu Yangyang Xu Yangyang Xu Wen-hai Feng Wen-hai Feng Wen-hai Feng Wen-hai Feng |
| author_sort | Siyuan Hao |
| collection | DOAJ |
| description | Cyclic GMP-AMP synthase (cGAS) recognizes viral DNA and synthesizes cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING/MITA) and downstream mediators to elicit an innate immune response. African swine fever virus (ASFV) proteins can antagonize host immune responses to promote its infection. Here, we identified ASFV protein QP383R as an inhibitor of cGAS. Specifically, we found that overexpression of QP383R suppressed type I interferons (IFNs) activation stimulated by dsDNA and cGAS/STING, resulting in decreased transcription of IFNβ and downstream proinflammatory cytokines. In addition, we showed that QP383R interacted directly with cGAS and promoted cGAS palmitoylation. Moreover, we demonstrated that QP383R suppressed DNA binding and cGAS dimerization, thus inhibiting cGAS enzymatic functions and reducing cGAMP production. Finally, the truncation mutation analysis indicated that the 284-383aa of QP383R inhibited IFNβ production. Considering these results collectively, we conclude that QP383R can antagonize host innate immune response to ASFV by targeting the core component cGAS in cGAS-STING signaling pathways, an important viral strategy to evade this innate immune sensor. |
| first_indexed | 2024-04-09T13:45:21Z |
| format | Article |
| id | doaj.art-9900af2b83e040c9a3bdd00be0abb681 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T13:45:21Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9900af2b83e040c9a3bdd00be0abb6812023-05-09T05:17:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.11869161186916African swine fever virus QP383R dampens type I interferon production by promoting cGAS palmitoylationSiyuan Hao0Siyuan Hao1Siyuan Hao2Siyuan Hao3Xiaojie Zheng4Xiaojie Zheng5Xiaojie Zheng6Xiaojie Zheng7Yingqi Zhu8Yingqi Zhu9Yingqi Zhu10Yingqi Zhu11Yao Yao12Yao Yao13Yao Yao14Yao Yao15Sihan Li16Sihan Li17Sihan Li18Sihan Li19Yangyang Xu20Yangyang Xu21Yangyang Xu22Yangyang Xu23Wen-hai Feng24Wen-hai Feng25Wen-hai Feng26Wen-hai Feng27State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaFrontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaMinistry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, ChinaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaFrontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaMinistry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, ChinaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaFrontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaMinistry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, ChinaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaFrontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaMinistry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, ChinaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaFrontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaMinistry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, ChinaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaFrontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaMinistry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, ChinaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaFrontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaMinistry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, ChinaCyclic GMP-AMP synthase (cGAS) recognizes viral DNA and synthesizes cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING/MITA) and downstream mediators to elicit an innate immune response. African swine fever virus (ASFV) proteins can antagonize host immune responses to promote its infection. Here, we identified ASFV protein QP383R as an inhibitor of cGAS. Specifically, we found that overexpression of QP383R suppressed type I interferons (IFNs) activation stimulated by dsDNA and cGAS/STING, resulting in decreased transcription of IFNβ and downstream proinflammatory cytokines. In addition, we showed that QP383R interacted directly with cGAS and promoted cGAS palmitoylation. Moreover, we demonstrated that QP383R suppressed DNA binding and cGAS dimerization, thus inhibiting cGAS enzymatic functions and reducing cGAMP production. Finally, the truncation mutation analysis indicated that the 284-383aa of QP383R inhibited IFNβ production. Considering these results collectively, we conclude that QP383R can antagonize host innate immune response to ASFV by targeting the core component cGAS in cGAS-STING signaling pathways, an important viral strategy to evade this innate immune sensor.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1186916/fullASFVQP383Rtype I interferonscGASpalmitoylation |
| spellingShingle | Siyuan Hao Siyuan Hao Siyuan Hao Siyuan Hao Xiaojie Zheng Xiaojie Zheng Xiaojie Zheng Xiaojie Zheng Yingqi Zhu Yingqi Zhu Yingqi Zhu Yingqi Zhu Yao Yao Yao Yao Yao Yao Yao Yao Sihan Li Sihan Li Sihan Li Sihan Li Yangyang Xu Yangyang Xu Yangyang Xu Yangyang Xu Wen-hai Feng Wen-hai Feng Wen-hai Feng Wen-hai Feng African swine fever virus QP383R dampens type I interferon production by promoting cGAS palmitoylation Frontiers in Immunology ASFV QP383R type I interferons cGAS palmitoylation |
| title | African swine fever virus QP383R dampens type I interferon production by promoting cGAS palmitoylation |
| title_full | African swine fever virus QP383R dampens type I interferon production by promoting cGAS palmitoylation |
| title_fullStr | African swine fever virus QP383R dampens type I interferon production by promoting cGAS palmitoylation |
| title_full_unstemmed | African swine fever virus QP383R dampens type I interferon production by promoting cGAS palmitoylation |
| title_short | African swine fever virus QP383R dampens type I interferon production by promoting cGAS palmitoylation |
| title_sort | african swine fever virus qp383r dampens type i interferon production by promoting cgas palmitoylation |
| topic | ASFV QP383R type I interferons cGAS palmitoylation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1186916/full |
| work_keys_str_mv | AT siyuanhao africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT siyuanhao africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT siyuanhao africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT siyuanhao africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT xiaojiezheng africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT xiaojiezheng africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT xiaojiezheng africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT xiaojiezheng africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT yingqizhu africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT yingqizhu africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT yingqizhu africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT yingqizhu africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT yaoyao africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT yaoyao africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT yaoyao africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT yaoyao africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT sihanli africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT sihanli africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT sihanli africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT sihanli africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT yangyangxu africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT yangyangxu africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT yangyangxu africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT yangyangxu africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT wenhaifeng africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT wenhaifeng africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT wenhaifeng africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation AT wenhaifeng africanswinefevervirusqp383rdampenstypeiinterferonproductionbypromotingcgaspalmitoylation |