CiLSM14Aa acts as a cytosolic dsRNA sensor to activate antiviral immunity against GCRV-II

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.