Global fish production from aquaculture has rapidly grown over the past decades, and grass carp shares the largest portion. However, hemorrhagic disease caused by grass carp reovirus (GCRV) results in tremendous loss of grass carp (Ctenopharyngodon idella) industry. During the past years, development of molecular biology and cellular biology technologies has promoted significant advances in the understanding of the pathogen and the immune system. Immunoprophylaxis based on stimulation of the immune system of fish has also got some achievements. In this review, authors summarize the recent progresses in basic researches on GCRV; viral nucleic acid sensors, high-mobility group box proteins (HMGBs); pattern recognition receptors (PRRs), Toll-like receptors (TLRs) and retinoic acid inducible gene I- (RIG-I-) like receptors (RLRs); antiviral immune responses induced by PRRs-mediated signaling cascades of type I interferon (IFN-I) and IFN-stimulated genes (ISGs) activation. The present review also notices the potential applications of molecule genetic markers. Additionally, authors discuss the current preventive and therapeutic strategies (vaccines, RNAi, and prevention medicine) and highlight the importance of innate immunity in long term control for grass carp hemorrhagic disease.

TLRs are pivotal pattern recognition receptors in initiating innate immunity and triggering adaptive immunity. TLR pathways have been comprehensively investigated in mammals. However, the teleost-specific TLR19 pathway remains largely unknown. In this study, we identified TLR19 from grass carp (Ctenopharyngodon idella), and explored the ligand, adaptor, and signaling pathways. Pathogen-associated molecular pattern binding and luciferase activity assays indicate that TLR19 recognizes and responds to dsRNA analog (polyinosinic:polycytidylic acid). Confocal fluorescence microscopy demonstrates that TLR19 is synthesized in ribosomes not binding on endoplasmic reticulum, then transfers to early endosome post-polyinosinic:polycytidylic acid stimulation. Fluorescence colocalization and immunoprecipitation experiments confirm TLR19 interacts with adaptor TRIF, not MyD88, TIRAP, or SARM1. TLR19 facilitates protein and phosphorylation levels of IRF3, inhibits phosphorylation of IRF7. TLR19 enhances the promoter activities and mRNA expressions of major IFNs and NF-κBs; in contrast, grass carp TLR3 just significantly motivates IFN1 expression post-grass carp reovirus (GCRV) infection. Further investigations reveal that TLR19 inhibits GCRV replication by overexpression, knockdown, Western blotting techniques and virus titer assays, and protects cells from GCRV infection by flow cytometry and MTT method. Collectively, these results demonstrate that teleost-specific TLR19 recognizes dsRNA, recruits adaptor molecule TRIF, enhances IRF3 protein and phosphorylation levels, triggers both IFN and NF-κB pathways, and prevents viral proliferation. This is the first attempt to systematically clarify the TLR19 signaling pathway, which is the third TLR member recognizing dsRNA. The results will serve the antiviral immune mechanisms in teleost and evolutionary immunology.