Frontiers in Immunology (May 2023)
African swine fever virus QP383R dampens type I interferon production by promoting cGAS palmitoylation
- 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
Affiliations
- Siyuan Hao
- State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Siyuan Hao
- Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Siyuan Hao
- Ministry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, China
- Siyuan Hao
- Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, China
- Xiaojie Zheng
- State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Xiaojie Zheng
- Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Xiaojie Zheng
- Ministry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, China
- Xiaojie Zheng
- Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, China
- Yingqi Zhu
- State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Yingqi Zhu
- Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Yingqi Zhu
- Ministry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, China
- Yingqi Zhu
- Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, China
- Yao Yao
- State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Yao Yao
- Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Yao Yao
- Ministry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, China
- Yao Yao
- Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, China
- Sihan Li
- State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Sihan Li
- Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Sihan Li
- Ministry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, China
- Sihan Li
- Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, China
- Yangyang Xu
- State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Yangyang Xu
- Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Yangyang Xu
- Ministry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, China
- Yangyang Xu
- Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, China
- Wen-hai Feng
- State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Wen-hai Feng
- Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, China
- Wen-hai Feng
- Ministry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, China
- Wen-hai Feng
- Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, China
- DOI
- https://doi.org/10.3389/fimmu.2023.1186916
- Journal volume & issue
-
Vol. 14
Abstract
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.
Keywords
