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...

Full description

Bibliographic Details
Main Authors: Wanglong Zheng, Nengwen Xia, Jiajia Zhang, Qi Cao, Sen Jiang, Jia Luo, Hui Wang, Nanhua Chen, Quan Zhang, François Meurens, Jianzhong Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.941579/full
_version_ 1818237015794122752
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
format Article
id doaj.art-85252b1cc1bb4fffab46b6183c7816c9
institution Directory Open Access Journal
issn 1664-3224
language English
last_indexed 2024-12-12T12:19:03Z
publishDate 2022-07-01
publisher Frontiers Media S.A.
record_format Article
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
work_keys_str_mv AT wanglongzheng africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT wanglongzheng africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT wanglongzheng africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT wanglongzheng africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT nengwenxia africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT nengwenxia africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT nengwenxia africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT nengwenxia africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT jiajiazhang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT jiajiazhang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT jiajiazhang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT jiajiazhang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT qicao africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT qicao africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT qicao africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT qicao africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT senjiang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT senjiang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT senjiang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT senjiang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT jialuo africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT jialuo africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT jialuo africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT jialuo africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT huiwang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT huiwang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT huiwang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT huiwang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT nanhuachen africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT nanhuachen africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT nanhuachen africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT nanhuachen africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT quanzhang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT quanzhang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT quanzhang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT quanzhang africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT francoismeurens africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT francoismeurens africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT jianzhongzhu africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT jianzhongzhu africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT jianzhongzhu africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting
AT jianzhongzhu africanswinefevervirusstructuralproteinp17inhibitscgasstingsignalingpathwaythroughinteractingwithsting