cGASa and cGASb from grass carp (Ctenopharyngodon idellus) play opposite roles in mediating type I interferon response

Xu, Xiaowen; Li, Meifeng; Deng, Zeyuan; Jiang, Zeyin; Li, Dongming; Wang, Shanghong; Hu, Chengyu

doi:10.1016/j.dci.2021.104233

Cited by 6 publications

(8 citation statements)

References 44 publications

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“…In mammals, only one type of cGAS is typically found and plays an important role in the activation of type I IFN ( 25 , 26 ). In fish, due to genome duplication events ( 27 ), two paralogs of cGAS were found in grass carp and zebrafish ( 28 , 29 ). However, only one cGAS has been recorded in grouper.…”

Section: Discussionmentioning

confidence: 99%

“…After SGIV infection, the expression of EccGAS increased with the time of virus infection, suggesting that EccGAS is involved in the innate immune response. Similarly, grass carp cGASa was up-regulated under GCRV or poly dA:dT treatment ( 28 ), and grass carp cGASb was up-regulated under GCRV, poly dA:dT or poly I:C treatment ( 28 , 35 ). Meanwhile, the Japanese medaka cGAS was significantly induced under Edwardsiella tarda treatment ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Zhang²,

Liao³

et al. 2023

Front. Immunol.

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Zhang

Zhang²,

Liao³

et al. 2023

Front. Immunol.

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“…In grass carp, two paralogs of cGAS gene namely cGASa and cGASb have been identified. Grass carp cGASa and MITA protected the cells from GCRV infection, but cGASb inhibited cGASa‐MITA signalling by competitive interaction with MITA 154 . Furthermore, piscine MARCH8 targets MITA for protein degradation, which facilitates viral replication of GCRV 155 .…”

Section: Immune Escape Mechanisms By Aqrvsmentioning

confidence: 99%

“…NS26 is not a FAST protein, however, NS26 could enhance the fusion activity by interacting with NS16. 94 A potential vacuolar targeting motif 151 TLPK 154 was identified in the amino acid sequence of NS26 by bioinformatics analysis, and deletion of the TLPK motif from NS26 significantly impaired the enhanced efficiency of the NS16-mediated cell-cell fusion by NS26. Furthermore, syncytiogenesis assay revealed that the conserved K 154 residue located within the TLPK motif was critical for NS26 to enhance the fusogenic activity of NS16.…”

Section: Ns26 As a Regulator For Fusogenic Activity And Viral Replica...mentioning

confidence: 99%

“…Grass carp cGASa and MITA protected the cells from GCRV infection, but cGASb inhibited cGASa-MITA signalling by competitive interaction with MITA. 154 Furthermore, piscine MARCH8 targets MITA for protein degradation, which facilitates viral replication of GCRV. 155 MITA is also a popular target of viral antagonists.…”

Section: The Replication and Infection Of Aqrvsmentioning

confidence: 99%

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Structure, function and immune evasion strategies of aquareoviruses, with focus on grass carp reovirus

Zhang

Chang

2023

Reviews in Aquaculture

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Aquareoviruses (AqRVs) can infect various wild or cultured bony fishes with serious muscle and viscera haemorrhage syndrome and have caused severe economic losses worldwide. Accumulating evidences have revealed the functions of viral proteins of AqRVs in RNA transcription, virion assembly, cell attachment and/or viral replication. In addition, structural information and transcription mechanism of AqRVs have been in‐depth studied through cryo‐electron microscopy combined with three‐dimensional image reconstruction. Although far from enough, structural and functional studies of AqRVs provide substantial insights into how viral proteins coordinate the replication of AqRVs and escape the host immune response. Grass carp reovirus (GCRV) is the most pathogenic AqRV isolated from aquatic animals. The completion of GCRV lifecycle requires the participation of host proteins. So far, many host factors involved in the entry and replication of GCRV have been identified. Based on the function of viral proteins and the viral lifecycle, many vaccines and antiviral agents have been developed to prevent the replication and infection of GCRV. This review summarises the structural characteristics and the composition of core proteins of AqRVs, as well as synergistic mechanisms of structural proteins on genome transcription and virus entry of AqRVs. In addition, the review highlights our current knowledge for the infection and replication, functions of non‐structural proteins, immune escape mechanisms, as well as the vaccines and antiviral agents of AqRVs, especially for GCRV. A better understanding of structure, function and immune evasion strategies of AqRVs will offer new targets for prevention and control of AqRVs in aquaculture.

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