Porcine IFI16 Negatively Regulates cGAS Signaling Through the Restriction of DNA Binding and Stimulation

被引:11
|
作者
Zheng, Wanglong [1 ,2 ,3 ,4 ]
Zhou, Rongyun [1 ,2 ,3 ,4 ]
Li, Shuangjie [1 ,2 ,3 ,4 ]
He, Shan [1 ,2 ,3 ,4 ]
Luo, Jia [1 ,2 ,3 ,4 ]
Zhu, Meiqin [1 ,2 ,3 ,4 ]
Chen, Nanhua [1 ,2 ,3 ,4 ]
Chen, Hongjun [5 ]
Meurens, Francois [6 ]
Zhu, Jianzhong [1 ,2 ,3 ,4 ]
机构
[1] Yangzhou Univ, Comparat Med Res Inst, Yangzhou, Peoples R China
[2] Yangzhou Univ, Coll Vet Med, Yangzhou, Peoples R China
[3] Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou, Peoples R China
[4] Joint Int Res Lab Agr & Agri Prod Safety, Yangzhou, Peoples R China
[5] Chinese Acad Agr Sci, Shanghai Vet Res Inst, Shanghai, Peoples R China
[6] Oniris, BIOEPAR, INRAE, Nantes, France
来源
FRONTIERS IN IMMUNOLOGY | 2020年 / 11卷
基金
中国国家自然科学基金;
关键词
innate immunity; DNA sensor; signaling; porcine; mutual relationship; INNATE IMMUNE SENSOR; I INTERFERON; CYTOSOLIC DNA; VIRAL-DNA; AIM2; INFLAMMASOME; ACTIVATION; RECOGNITION; ADAPTER; HELICASE; AMP;
D O I
10.3389/fimmu.2020.01669
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The innate immunity DNA sensors have drawn much attention due to their significant importance against the infections with DNA viruses and intracellular bacteria. Among the multiple DNA sensors, IFI16, and cGAS are the two major ones, subjected to extensive studies. However, these two DNA sensors in livestock animals have not been well defined. Here, we studied the porcine IFI16 and cGAS, and their mutual relationship. We found that both enable STING-dependent signaling to downstream IFN upon DNA transfection and HSV-1 infection, and cGAS plays a major role in DNA signaling. In terms of their relationship, IFI16 appeared to interfere with cGAS signaling as deduced from both transfected and knockout cells. Mechanistically, IFI16 competitively binds with agonist DNA and signaling adaptor STING and thereby influences second messenger cGAMP production and downstream gene transcription. Furthermore, the HIN2 domain of porcine IFI16 harbored most of its activity and mediated cGAS inhibition. Thus, this study provides a unique insight into the porcine DNA sensing system.
引用
收藏
页数:13
相关论文
共 40 条
  • [21] Porcine bocavirus NP1 negatively regulates interferon signaling pathway by targeting the DNA-binding domain of IRF9
    Zhang, Ruoxi
    Fang, Liurong
    Wang, Dang
    Cai, Kaimei
    Zhang, Huan
    Xie, Lilan
    Li, Yi
    Chen, Huanchun
    Xiao, Shaobo
    VIROLOGY, 2015, 485 : 414 - 421
  • [22] The IFI16 restriction factor cooperates with HCMV pUL83 to down-regulate UL54 gene expression and viral DNA synthesis
    Biolatti, Matteo
    Pautasso, Sara
    Dell'Oste, Valentina
    De Andrea, Marco
    von Einem, Jens
    Plachter, Bodo
    Marschall, Manfred
    Gariglio, Maria
    Landolfo, Santo
    CYTOKINE, 2015, 76 (01) : 70 - 71
  • [23] ER-α negatively regulates TGF-β signaling by blocking Smad4 binding to DNA
    Wu, Y
    Wu, L
    Gathings, WE
    Cao, X
    JOURNAL OF BONE AND MINERAL RESEARCH, 2003, 18 : S19 - S19
  • [24] siRNA enhances DNA-mediated interferon lambda-1 response through crosstalk between RIG-I and IFI16 signalling pathway
    Sui, Hongyan
    Zhou, Ming
    Chen, Qian
    Lane, H. Clifford
    Imamichi, Tomozumi
    NUCLEIC ACIDS RESEARCH, 2014, 42 (01) : 583 - 598
  • [25] RETRACTED: BRCA1 Regulates IFI16 Mediated Nuclear Innate Sensing of Herpes Viral DNA and Subsequent Induction of the Innate Inflammasome and Interferon-β Responses (Retracted Article)
    Dutta, Dipanjan
    Dutta, Sujoy
    Veettil, Mohanan Valiya
    Roy, Arunava
    Ansari, Mairaj Ahmed
    Iqbal, Jawed
    Chikoti, Leela
    Kumar, Binod
    Johnson, Karen E.
    Chandran, Bala
    PLOS PATHOGENS, 2015, 11 (06)
  • [26] Hedgehog signaling regulates transcription through cubitus interruptus, a sequence-specific DNA binding protein
    VonOhlen, T
    Lessing, D
    Nusse, R
    Hooper, JE
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (06) : 2404 - 2409
  • [27] Yersinia YopJ negatively regulates IRF3-mediated antibacterial response through disruption of STING-mediated cytosolic DNA signaling
    Cao, Ye
    Guan, Kai
    He, Xiang
    Wei, Congwen
    Zheng, Zirui
    Zhang, Yanhong
    Ma, Shengli
    Zhong, Hui
    Shi, Wei
    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2016, 1863 (12): : 3148 - 3159
  • [28] RETRACTION: BRCA1 Regulates IFI16 Mediated Nuclear Innate Sensing of Herpes Viral DNA and Subsequent Induction of the Innate Inflammasome and Interferon-β Responses (Retraction of Vol 11, art no E1005030, 2015)
    Dutta, D.
    Dutta, S.
    Veettil, M. V.
    Roy, A.
    Ansari, M. A.
    Iqbal, J.
    PLOS PATHOGENS, 2022, 18 (10)
  • [29] RETRACTION: BRCA1 Regulates IFI16 Mediated Nuclear Innate Sensing of Herpes Viral DNA and Subsequent Induction of the Innate Inflammasome and Interferon-beta Responses (Retraction of Vol 11, art no E1005030, 2015)
    Dutta, D.
    Dutta, S.
    Veettil, M. V.
    Roy, A.
    Ansari, M. A.
    Iqbal, J.
    PLOS ONE, 2022, 17 (10):
  • [30] Extracellular DEK Regulates Hematopoiesis through CXCR2-Mediated Intracellular Signaling That Does Not Require Its Translocation into the Nucleus or Binding to DNA
    Capitano, Maegan
    Mor-Vaknin, Nirit
    Legendre, Maureen
    Cooper, Scott
    Kappes, Ferdinand
    Markovitz, David
    Broxmeyer, Hal E.
    BLOOD, 2017, 130