PTPN2 modulates antiviral immunity in grouper by promoting TBK1 degradation and suppressing interferon signaling

As a member of the class I non-receptor protein tyrosine phosphatase family, Tyrosine-protein phosphatase non-receptor type 2 (PTPN2) plays a pivotal role in the regulation of cellular signaling pathways. In this study, we successfully cloned and characterized a PTPN2 homolog from Epinephelus coioides, designated as EcPTPN2. The open reading frame (ORF) of EcPTPN2 spans 1186 nucleotides, encoding a protein of 395 amino acids (Accession number: PV289599). Sequence analysis revealed that EcPTPN2 contains the conserved PTPc domain and exhibits high sequence homology with Cottoperca gobio (93.40 %) and Chelmon rostratus (92.13 %). EcPTPN2 exhibited ubiquitous expression across all examined tissues, with particularly high expression levels observed in the head kidney, spleen, and brain. Subcellular localization analysis revealed that EcPTPN2 was predominantly localized in the nucleus of grouper spleen (GS) cells. Ectopic expression of EcPTPN2 significantly enhanced the replication of Singapore grouper iridovirus (SGIV) in GS cells. EcPTPN2 was found to modulate the cGAS-STING signaling pathway by attenuating its stimulatory effect on IFN3 promoter activity. EcPTPN2 was demonstrated to interact with EcTBK1 through Co-IP analysis. Ectopic expression of EcPTPN2 facilitated the degradation of exogenous EcTBK1, resulting in a dose-dependent reduction of EcTBK1 protein levels. These findings provide valuable insights into the innate immune mechanisms of grouper against viral infections, offering a molecular basis for understanding host-pathogen interactions in this economically important marine species.