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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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Autores principales: Zheng, Wanglong, Xia, Nengwen, Zhang, Jiajia, Cao, Qi, Jiang, Sen, Luo, Jia, Wang, Hui, Chen, Nanhua, Zhang, Quan, Meurens, François, Zhu, Jianzhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283692/
https://www.ncbi.nlm.nih.gov/pubmed/35844609
http://dx.doi.org/10.3389/fimmu.2022.941579
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author Zheng, Wanglong
Xia, Nengwen
Zhang, Jiajia
Cao, Qi
Jiang, Sen
Luo, Jia
Wang, Hui
Chen, Nanhua
Zhang, Quan
Meurens, François
Zhu, Jianzhong
author_facet Zheng, Wanglong
Xia, Nengwen
Zhang, Jiajia
Cao, Qi
Jiang, Sen
Luo, Jia
Wang, Hui
Chen, Nanhua
Zhang, Quan
Meurens, François
Zhu, Jianzhong
author_sort Zheng, Wanglong
collection PubMed
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.
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spelling pubmed-92836922022-07-16 African Swine Fever Virus Structural Protein p17 Inhibits cGAS-STING Signaling Pathway Through Interacting With STING Zheng, Wanglong Xia, Nengwen Zhang, Jiajia Cao, Qi Jiang, Sen Luo, Jia Wang, Hui Chen, Nanhua Zhang, Quan Meurens, François Zhu, Jianzhong Front Immunol Immunology 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. Frontiers Media S.A. 2022-07-01 /pmc/articles/PMC9283692/ /pubmed/35844609 http://dx.doi.org/10.3389/fimmu.2022.941579 Text en Copyright © 2022 Zheng, Xia, Zhang, Cao, Jiang, Luo, Wang, Chen, Zhang, Meurens and Zhu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zheng, Wanglong
Xia, Nengwen
Zhang, Jiajia
Cao, Qi
Jiang, Sen
Luo, Jia
Wang, Hui
Chen, Nanhua
Zhang, Quan
Meurens, François
Zhu, Jianzhong
African Swine Fever Virus Structural Protein p17 Inhibits cGAS-STING Signaling Pathway Through Interacting With STING
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 Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283692/
https://www.ncbi.nlm.nih.gov/pubmed/35844609
http://dx.doi.org/10.3389/fimmu.2022.941579
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