African Swine Fever Virus Structural Protein p17 Inhibits cGAS-STING Signaling Pathway Through Interacting With STING
African swine fever virus (ASFV) encodes more than 150 proteins, which establish complex interactions with the host for the benefit of the virus in order to evade the host’s defenses. However, currently, there is still a lack of information regarding the roles of the viral proteins in host cells. He...
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Frontiers Media S.A.
2022-07-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.941579/full |
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author | Wanglong Zheng Wanglong Zheng Wanglong Zheng Wanglong Zheng Nengwen Xia Nengwen Xia Nengwen Xia Nengwen Xia Jiajia Zhang Jiajia Zhang Jiajia Zhang Jiajia Zhang Qi Cao Qi Cao Qi Cao Qi Cao Sen Jiang Sen Jiang Sen Jiang Sen Jiang Jia Luo Jia Luo Jia Luo Jia Luo Hui Wang Hui Wang Hui Wang Hui Wang Nanhua Chen Nanhua Chen Nanhua Chen Nanhua Chen Quan Zhang Quan Zhang Quan Zhang Quan Zhang François Meurens François Meurens Jianzhong Zhu Jianzhong Zhu Jianzhong Zhu Jianzhong Zhu |
author_facet | Wanglong Zheng Wanglong Zheng Wanglong Zheng Wanglong Zheng Nengwen Xia Nengwen Xia Nengwen Xia Nengwen Xia Jiajia Zhang Jiajia Zhang Jiajia Zhang Jiajia Zhang Qi Cao Qi Cao Qi Cao Qi Cao Sen Jiang Sen Jiang Sen Jiang Sen Jiang Jia Luo Jia Luo Jia Luo Jia Luo Hui Wang Hui Wang Hui Wang Hui Wang Nanhua Chen Nanhua Chen Nanhua Chen Nanhua Chen Quan Zhang Quan Zhang Quan Zhang Quan Zhang François Meurens François Meurens Jianzhong Zhu Jianzhong Zhu Jianzhong Zhu Jianzhong Zhu |
author_sort | Wanglong Zheng |
collection | DOAJ |
description | African swine fever virus (ASFV) encodes more than 150 proteins, which establish complex interactions with the host for the benefit of the virus in order to evade the host’s defenses. However, currently, there is still a lack of information regarding the roles of the viral proteins in host cells. Here, our data demonstrated that ASFV structural protein p17 exerts a negative regulatory effect on cGAS-STING signaling pathway and the STING signaling dependent anti-HSV1 and anti-VSV functions. Further, the results indicated that ASFV p17 was located in ER and Golgi apparatus, and interacted with STING. ASFV p17 could interfere the STING to recruit TBK1 and IKKϵ through its interaction with STING. It was also suggested that the transmembrane domain (amino acids 39–59) of p17 is required for interacting with STING and inhibiting cGAS-STING pathway. Additionally, with the p17 specific siRNA, the ASFV induced IFN-β, ISG15, ISG56, IL-6 and IL-8 gene transcriptions were upregulated in ASFV infected primary porcine alveolar macrophages (PAMs). Taken together, ASFV p17 can inhibit the cGAS-STING pathway through its interaction with STING and interference of the recruitment of TBK1 and IKKϵ. Our work establishes the role of p17 in the immune evasion and thus provides insights on ASFV pathogenesis. |
first_indexed | 2024-12-12T12:19:03Z |
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language | English |
last_indexed | 2024-12-12T12:19:03Z |
publishDate | 2022-07-01 |
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series | Frontiers in Immunology |
spelling | doaj.art-85252b1cc1bb4fffab46b6183c7816c92022-12-22T00:24:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.941579941579African Swine Fever Virus Structural Protein p17 Inhibits cGAS-STING Signaling Pathway Through Interacting With STINGWanglong Zheng0Wanglong Zheng1Wanglong Zheng2Wanglong Zheng3Nengwen Xia4Nengwen Xia5Nengwen Xia6Nengwen Xia7Jiajia Zhang8Jiajia Zhang9Jiajia Zhang10Jiajia Zhang11Qi Cao12Qi Cao13Qi Cao14Qi Cao15Sen Jiang16Sen Jiang17Sen Jiang18Sen Jiang19Jia Luo20Jia Luo21Jia Luo22Jia Luo23Hui Wang24Hui Wang25Hui Wang26Hui Wang27Nanhua Chen28Nanhua Chen29Nanhua Chen30Nanhua Chen31Quan Zhang32Quan Zhang33Quan Zhang34Quan Zhang35François Meurens36François Meurens37Jianzhong Zhu38Jianzhong Zhu39Jianzhong Zhu40Jianzhong Zhu41College Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou, ChinaComparative Medicine Research Institute, Yangzhou University, Yangzhou, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, ChinaCollege Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou, ChinaComparative Medicine Research Institute, Yangzhou University, Yangzhou, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, ChinaCollege Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou, ChinaComparative Medicine Research Institute, Yangzhou University, Yangzhou, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, ChinaCollege Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou, ChinaComparative Medicine Research Institute, Yangzhou University, Yangzhou, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, ChinaCollege Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou, ChinaComparative Medicine Research Institute, Yangzhou University, Yangzhou, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, ChinaCollege Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou, ChinaComparative Medicine Research Institute, Yangzhou University, Yangzhou, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, ChinaCollege Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou, ChinaComparative Medicine Research Institute, Yangzhou University, Yangzhou, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, ChinaCollege Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou, ChinaComparative Medicine Research Institute, Yangzhou University, Yangzhou, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, ChinaCollege Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou, ChinaComparative Medicine Research Institute, Yangzhou University, Yangzhou, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, ChinaBIOEPAR, INRAE, Oniris, Nantes, FranceDepartment of Veterinary Microbiology and Immunology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, CanadaCollege Veterinary Medicine, Yangzhou University, Yangzhou, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou, ChinaComparative Medicine Research Institute, Yangzhou University, Yangzhou, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, ChinaAfrican swine fever virus (ASFV) encodes more than 150 proteins, which establish complex interactions with the host for the benefit of the virus in order to evade the host’s defenses. However, currently, there is still a lack of information regarding the roles of the viral proteins in host cells. Here, our data demonstrated that ASFV structural protein p17 exerts a negative regulatory effect on cGAS-STING signaling pathway and the STING signaling dependent anti-HSV1 and anti-VSV functions. Further, the results indicated that ASFV p17 was located in ER and Golgi apparatus, and interacted with STING. ASFV p17 could interfere the STING to recruit TBK1 and IKKϵ through its interaction with STING. It was also suggested that the transmembrane domain (amino acids 39–59) of p17 is required for interacting with STING and inhibiting cGAS-STING pathway. Additionally, with the p17 specific siRNA, the ASFV induced IFN-β, ISG15, ISG56, IL-6 and IL-8 gene transcriptions were upregulated in ASFV infected primary porcine alveolar macrophages (PAMs). Taken together, ASFV p17 can inhibit the cGAS-STING pathway through its interaction with STING and interference of the recruitment of TBK1 and IKKϵ. Our work establishes the role of p17 in the immune evasion and thus provides insights on ASFV pathogenesis.https://www.frontiersin.org/articles/10.3389/fimmu.2022.941579/fullAfrican swine fever virusp17 proteincGAS-STING pathwayTBK1IKKϵ |
spellingShingle | Wanglong Zheng Wanglong Zheng Wanglong Zheng Wanglong Zheng Nengwen Xia Nengwen Xia Nengwen Xia Nengwen Xia Jiajia Zhang Jiajia Zhang Jiajia Zhang Jiajia Zhang Qi Cao Qi Cao Qi Cao Qi Cao Sen Jiang Sen Jiang Sen Jiang Sen Jiang Jia Luo Jia Luo Jia Luo Jia Luo Hui Wang Hui Wang Hui Wang Hui Wang Nanhua Chen Nanhua Chen Nanhua Chen Nanhua Chen Quan Zhang Quan Zhang Quan Zhang Quan Zhang François Meurens François Meurens Jianzhong Zhu Jianzhong Zhu Jianzhong Zhu Jianzhong Zhu African Swine Fever Virus Structural Protein p17 Inhibits cGAS-STING Signaling Pathway Through Interacting With STING Frontiers in Immunology African swine fever virus p17 protein cGAS-STING pathway TBK1 IKKϵ |
title | African Swine Fever Virus Structural Protein p17 Inhibits cGAS-STING Signaling Pathway Through Interacting With STING |
title_full | African Swine Fever Virus Structural Protein p17 Inhibits cGAS-STING Signaling Pathway Through Interacting With STING |
title_fullStr | African Swine Fever Virus Structural Protein p17 Inhibits cGAS-STING Signaling Pathway Through Interacting With STING |
title_full_unstemmed | African Swine Fever Virus Structural Protein p17 Inhibits cGAS-STING Signaling Pathway Through Interacting With STING |
title_short | African Swine Fever Virus Structural Protein p17 Inhibits cGAS-STING Signaling Pathway Through Interacting With STING |
title_sort | african swine fever virus structural protein p17 inhibits cgas sting signaling pathway through interacting with sting |
topic | African swine fever virus p17 protein cGAS-STING pathway TBK1 IKKϵ |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.941579/full |
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