Grouper cGAS is a negative regulator of STING-mediated interferon response

Front Immunol. 2023 Feb 7:14:1092824. doi: 10.3389/fimmu.2023.1092824. eCollection 2023.

Abstract

Cyclic GMP-AMP synthase (cGAS) is one of the classical pattern recognition receptors that recognizes mainly intracytoplasmic DNA. cGAS induces type I IFN responses to the cGAS-STING signaling pathway. To investigate the roles of cGAS-STING signaling pathway in grouper, a cGAS homolog (named EccGAS) was cloned and identified from orange-spotted grouper (Epinephelus coioides). The open reading frame (ORF) of EccGAS is 1695 bp, encodes 575 amino acids, and contains a Mab-21 typical structural domain. EccGAS is homologous to Sebastes umbrosus and humans at 71.8% and 41.49%, respectively. EccGAS mRNA is abundant in the blood, skin, and gills. It is uniformly distributed in the cytoplasm and colocalized in the endoplasmic reticulum and mitochondria. Silencing of EccGAS inhibited the replication of Singapore grouper iridovirus (SGIV) in grouper spleen (GS) cells and enhanced the expression of interferon-related factors. Furthermore, EccGAS inhibited EcSTING-mediated interferon response and interacted with EcSTING, EcTAK1, EcTBK1, and EcIRF3. These results suggest that EccGAS may be a negative regulator of the cGAS-STING signaling pathway of fish.

Keywords: CGAS; Epinephelus coioides; SGIV; STING; virus replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bass* / genetics
  • Humans
  • Interferon Type I*
  • Perciformes*
  • Ranavirus* / physiology

Substances

  • Interferon Type I

Grants and funding

This research was funded by the National Key Research and Development Program of China (2022YFD2400501), Key-Area Research and Development Program of Guangdong Province (2021B0202040002), Laboratory of Lingnan Modern Agriculture Project (NT2021008), the China Agriculture Research System of MOF and MARA(CARS-47-G16), the Agricultural Science and Technology Cooperation Project of Institute of New Rural Development of South China Agricultural University (2021XNYNYKJHZGJ042), and Open Fund of Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy culture (PBEA2020YB01).