4.7 Article

Characterization of STING from common carp (Cyprinus carpio L.) involved in spring viremia of carp virus infection

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FISH & SHELLFISH IMMUNOLOGY
卷 142, 期 -, 页码 -

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ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fsi.2023.109164

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Cyprinus carpio L.; Stimulator of the interferon genes; Spring viremia of carp virus; Gene expression; IFN response

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This study cloned and characterized common carp STING (CcSTING), and found that it plays a critical role in the immune response against RNA viruses. CcSTING is mainly located in the cytoplasm within the endoplasmic reticulum, and has strong expression in organs such as gills and head kidney. Additionally, overexpression of CcSTING can significantly suppress the replication of SVCV in EPC cells, likely through enhancing IFN and NF-κB activity and up-regulating the phosphorylation of TBK1 and p65.
Stimulator of interferon genes (STING) serve as an endoplasmic reticulum (ER) protein and modulates innate immune responses to viral contagion. Most investigations involving teleost STING antiviral immunity have examined DNA viruses. Therefore, fish STING signaling events against RNA viruses require additional exploration. Here, common carp STING (named CcSTING) was cloned and characterized. The bioinformatics analyses of CcSTING showed evolutionary conservations and were most closely related to other cyprinid STINGs. Immunofluorescence staining discovered that the CcSTING was chiefly placed in the cytoplasm, specifically within the ER. CcSTING was ubiquitously generated in all analyzed organs, with especially strong expression in the gills and head kidney. Spring viremia of carp virus (SVCV) stimulation and poly(I:C) infection induced the generation of CcSTING in immune-associated organs, as well as in peripheral blood leukocytes. Additional investigations revealed that CcSTING overexpression strongly suppressed SVCV replication in EPC cells. Mechanistically, CcSTING enhanced IFN-1 and ISGs expression following SVCV infection. CcSTING also substantially increased both IFN and NF-kappa B promoter luciferase activity via a dosage-dependent fashion. Lastly, CcSTING significantly up-regulated both TBK1 and p65 phosphorylation. Collectively, these findings demonstrated the critical role and underlying mechanism of fish STING in response to RNA virus.

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