SGIV evades interferon immune response via the degradation of STING-TBK1 complex by VP149.

Singapore grouper iridovirus (SGIV), a highly pathogenic member of iridoviruses, has become a global threat in the aquaculture industry due to its economic losses and damage to ecological diversity worldwide. Recent reports have shown that SGIV inhibits host interferon (IFN) immune response induced by poly(I:C), however, the potential mechanisms for immune evasion remain largely uncertain. Here, VP149 protein encoded by SGIV ORF149R was identified to be a pro-viral factor, evidenced by the increase of SGIV gene expression and viral production in VP149-overexpressing cells. SGIV VP149 overexpression suppressed IFN-1 and ISRE promoter activation, and the transcription of IFN-stimulated genes triggered by Epinephelus coioides stimulator of IFN genes (EcSTING), TANK-binding kinase 1 (EcTBK1), melanoma differentiation-associated gene 5 (EcMDA5), or mitochondrial antiviral signaling protein (EcMAVS). Mutational analyses suggested that VP149 interacted with EcSTING and EcTBK1, and their interactions were not dependent on the domains of adaptor protein. In addition, VP149 impaired EcSTING-EcTBK1 or EcTBK1-EcIRF3 (interferon regulatory factor 3) complex formations, and degraded EcSTING or EcTBK1 through the lysosome pathway to promote red-spotted grouper nervous necrosis virus (RGNNV) infection. Collectively, a novel mechanism through which SGIV evaded fish immune via its protein VP149 by targeting STING and TBK1 to suppress type I IFN expression was revealed, and the findings will provide insights into pathogenesis and prevention of SGIV. • SGIV-encoded protein VP149 was identified to be a pro-viral factor. • VP149 interacted with EcSTING and EcTBK1 to suppress type I interferon expression triggered by EcSTING, and EcTBK1. • VP149 impaired EcSTING-EcTBK1 or EcTBK1-EcIRF3 association. • VP149 degraded EcSTING or EcTBK1 in a dose manner through the lysosome pathway. [ABSTRACT FROM AUTHOR]