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Cyprinid herpesvirus 2 (CyHV-2) caused hematopoietic necrosis in crucian carp (Carassius auratus) has resulted in huge economic losses to the carp aquaculture. Interferon (IFN) response serves as a crucial line of defense for fish against CyHV-2 infection; however, CyHV-2 frequently overcomes this defense, resulting in damage and even substantial mortality. The mechanism by which CyHV-2 evades the fish IFN antiviral response remains unclear. In this study, we chose the open reading frame 67 (ORF67) of CyHV-2 as the target of our research. Firstly, the results of Co-immunoprecipitation (Co-IP) assay and in vitro phosphorylation showed that the ORF67 inhibited the expression of IFN by binding to TBK1-A/B and competitively blocking STING-A/B phosphorylation. Then, we elaborated on the effect of ORF67 on the cell's antiviral function by cytopathic effect (CPE) and immunoblot analysis. In summary, this study has clarified the molecular mechanism of immune evasion by ORF67 through the inhibition of host IFN expression. This research enhances our understanding of the pathogenesis of CyHV-2 and provides theoretical references for the prevention and treatment of hematopoietic necrosis.
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http://dx.doi.org/10.1016/j.fsi.2025.110372 | DOI Listing |
Fish Shellfish Immunol
August 2025
College of Fisheries, Hunan Agricultural University, Changsha, 410128, China. Electronic address:
Mammalian cyclic GMP-AMP synthetase (cGAS) exerts a pivotal role in innate immune response to viral infection by detecting viral DNA and activating the cGAS-STING pathway, which triggers type I interferon (IFN-I) production. Although cGAS has been widely investigated in mammals, its function in lower vertebrates, especially in teleost fish, remains poorly understood. Herein, a cGAS homolog (termed c-cGAS) in common carp was identified and functionally characterized to explore its involvement in immune activation and viral response.
View Article and Find Full Text PDFFish Shellfish Immunol
August 2025
National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, Shanghai, 201306, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, 201306, China; Key Laboratory of Freshwater Aquatic Genetic Resources, Ministr
Cyprinid herpesvirus 2 (CyHV-2), a virus that triggers Herpesvirus Hematopoietic Necrosis Disease, presents a major challenge for goldfish and related species. Previous studies have reported that quercetin inhibits viral replication by suppressing phosphorylation of AKT, the core protein of the PI3K/AKT signaling pathway. This study further found that quercetin also has anti-CyHV-2 effects in vivo.
View Article and Find Full Text PDFScience
July 2025
Innate Immunity in Physiology and Cancer Team, Institut Curie, PSL Research University, INSERM U932, Paris, France.
Key actors of mammalian immunity originated from bacterial antiphage systems. The full extent of immune system conservation between bacteria and eukaryotes is unknown. Here, we show that the silent information regulator 2 (SIR2) protein domain, present in antiphage systems, plays a role in eukaryotic innate immunity.
View Article and Find Full Text PDFBMC Genomics
July 2025
State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Hubei Hongshan Laboratory, The Innovation Academy of Seed Design, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
Allopolyploids often exhibit enhanced resistance to pathogen stresses. However, our understanding about the patterns that allopolyploids modify homeolog expression upon pathogen invasion remains limited. Since 2012, a disease caused by herpesvirus (CaHV) has posed a severe threat to Carassius auratus aquaculture.
View Article and Find Full Text PDFJ Fish Dis
July 2025
National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, Shanghai, China.
Crucian carp (Carassius auratus gibelio) is sensitive to the infection of Cyprinid herpesvirus 2 (CyHV-2), displaying severe inflammatory reactions characterised by systemic congestion and gill bleeding. This study aimed to elucidate the mechanism by which CyHV-2 infection induces interferon gamma (IFNγ) expression in caudal fin cells (GiCF) of Carassius auratus gibelio, specifically investigating the role of the IL-17C/NF-κB signalling axis. In mammalian systems, virus-induced IL-17 has been demonstrated to activate NF-κB, a master regulator of inflammatory responses that controls multiple antiviral immune genes including interferons.
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