Singapore grouper iridovirus VP018 abrogates the interferon response by targeting STING-TBK1-IRF3 axis.

Singapore grouper iridovirus (SGIV), causes high mortality rate in grouper aquaculture. Previous study showed that SGIV VP018 was a highly abundant virulence factor, but the potential mechanism underlying the actions of VP018 still remained largely uncertain. Here, we firstly demonstrated that VP018 was interacted with major capsid protein (MCP) and VP075, and recruited into viral assembly sites in SGIV infected cells. Of note, VP018 was identified as a novel iridoviral protein that interacted with TANK-binding kinase 1 (EcTBK1) and IFN regulatory factor 3 (EcIRF3) by yeast two-hybrid screening and co-immunoprecipitation assay. In addition, the adaptor protein stimulator of interferon genes (EcSTING) was also found to interact with VP018. Furthermore, VP018 degraded EcSTING, EcTBK1 and EcIRF3 proteins in vitro, and suppressed their induction of interferon response. VP018 also disrupted the formation of EcSTING-EcTBK1 and EcTBK1-EcIRF3 complexes, leading to the reduction of EcIRF3 nuclear translocation. In addition, VP018 negatively regulated the antiviral actions of EcSTING, EcTBK1 and EcIRF3 against red-spotted grouper nervous necrosis virus (RGNNV) infection. Together, our findings provided the evidence that VP018 was involved in SGIV assembly, but also firstly demonstrated that VP018 functioned as a novel immune evasion protein which antagonized the host antiviral response via STING-TBK1-IRF3 axis.