Rainbow trout (Oncorhynchus mykiss) G3BP1 function as an antiviral molecule against infectious hematopoietic necrosis virus infection.

The Ras-GTPase activating protein (SH3 domain)-binding protein 1 (G3BP1) is an RNA-binding protein involved in mammalian cellular stress responses and antiviral immunity, playing a central role in stress granule (SG) assembly. However, its function in lower vertebrates remains poorly understood. In this study, we cloned and characterized G3BP1 from rainbow trout (Oncorhynchus mykiss), designated OmG3BP1, and investigated its role during infectious hematopoietic necrosis virus (IHNV) infection. The open reading frame of OmG3BP1 encoded a protein of 489 amino acids, with a predicted molecular mass of 54.06 kDa. OmG3BP1 contains five conserved functional domains and clusters phylogenetically with other fish orthologs. OmG3BP1 was ubiquitously expressed in all examined tissues, with the highest levels detected in muscle, liver, and heart. In vitro, OmG3BP1 overexpression significantly suppressed the replication of IHNV and was associated with increased expression of interferon-related genes. Knockdown of OmG3BP1 by siRNA significantly enhanced viral replication, further confirming its antiviral role. Furthermore, we demonstrated that IHNV infection induces SG formation in RTG-2 cells through phosphorylation of the eukaryotic initiation factor 2α (eIF2α). Our findings reveal that OmG3BP1 exerts antiviral activity against IHNV and provide new insights for IHNV pathogenesis and antiviral drug research.