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Journal of General Virology header logo Journal of General Virology

Volume 105, Issue 10

Singapore grouper iridovirus VP12 evades the host antiviral immune response by targeting the cGAS-STING signalling pathway No Access

Abstract

The emergence of Singapore grouper iridovirus (SGIV) has caused huge losses to grouper farming. SGIV is a DNA virus and belongs to the genus . Groupers infected with SGIV showed haemorrhaging and swelling of the spleen, with a mortality rate of more than 90% within a week. Therefore, it is of great significance to study the escape mechanism of SGIV from host innate immunity for the prevention and treatment of viral diseases in grouper. In this study, the viral proteins that interact with EccGAS were identified by mass spectrometry, and the SGIV VP12 protein that inhibits cyclic GMP–AMP synthase (cGAS)-stimulator of interferon genes (STING)-mediated antiviral innate immunity was screened by the dual-luciferase reporter gene assay. VP12 belongs to the late gene of the virus. The immunofluorescence analysis demonstrated that VP12 was aggregated and distributed in the cytoplasm during the early stage of virus infection and translocated into the nucleus at the late stage of virus infection. VP12 inhibited the activation of IFN3, ISRE and NF-κB promoter activities mediated by cGAS-STING, EcTBK1 and EcIRF3. Quantitative real-time PCR analysis showed that VP12 inhibited the expression of interferon-related genes, including those mediated by cGAS-STING. VP12 enhanced the inhibition of IFN3, ISRE and NF-κB promoter activity by EccGAS, EccGAS-mab-21 and EccGAS-delete-mab21. The interaction between VP12 and EccGAS was found to be domain independent. The immunoprecipitation results demonstrated that VP12 interacted and co-localized with EccGAS, EcTBK1 and EcIRF3. VP12 degraded the protein levels of EcTBK1 and EcIRF3 and degraded EcIRF3 through the protease pathway. These results suggest that SGIV VP12 protein escapes the cGAS-STING signalling pathway and degrades EcIRF3 protein expression through the protease pathway.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): cGAS–STING , Epinephelus coioides , SGIV and VP12
Funding
This study was supported by the:
  • Agriculture Research System of China (Award CARS-47-G16)
    • Principal Award Recipient: QiweiQin
  • Guangzhou Municipal Science and Technology Program key projects (Award 2023E04J0137)
    • Principal Award Recipient: JingguangWei
  • Guangdong Provincial Applied Science and Technology Research and Development Program (Award 2021B0202040002)
    • Principal Award Recipient: QiweiQin
  • Key Technologies Research and Development Program (Award 2022YFD2400501)
    • Principal Award Recipient: JingguangWei
  • Key Technologies Research and Development Program (Award 2023YFC2812100)
    • Principal Award Recipient: QiweiQin
© 2024 The Authors
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2024-10-11
2025-12-07

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/content/journal/jgv/10.1099/jgv.0.002031
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Singapore grouper iridovirus VP12 evades the host antiviral immune response by targeting the cGAS-STING signalling pathway
J. Gen. Virol. 105, 002031 (2024); https://doi.org/10.1099/jgv.0.002031
/content/journal/jgv/10.1099/jgv.0.002031
/content/journal/jgv/10.1099/jgv.0.002031
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