Abstract

The innate immune system relies on pattern recognition receptors (PRRs) to detect viral pathogens and initiate antiviral responses. LSM14A, a conserved RNA-binding protein involved in mRNA metabolism, has recently emerged as a cytosolic nucleic acid sensor in vertebrates. However, its role in teleost immunity remains unclear. In this study, two LSM14A paralogs were identified in grass carp ( Ctenopharyngodon idella ), designated CiLSM14Aa and CiLSM14Ab, and their functions during infection with grass carp reovirus genotype II (GCRV-II) were investigated. Both CiLSM14Aa and CiLSM14Ab were significantly upregulated following GCRV-II infection or poly(I:C) stimulation. Overexpression of CiLSM14Aa or CiLSM14Ab inhibited GCRV-II replication and enhanced the expression of type I interferon and interferon-stimulated genes (ISGs). Further analysis revealed that CiLSM14Aa and CiLSM14Ab can form homodimers and heterodimers. Notably, only CiLSM14Aa demonstrated direct binding to double-stranded RNA (dsRNA), suggesting a specific role as a cytosolic dsRNA sensor. These results demonstrate the essential antiviral roles of CiLSM14A paralogs and reveal their contributions to the initiation of innate immune defenses against GCRV-II infection.