Host interaction of tumor necrosis factor receptors encoded by Carassius auratus herpesvirus

Carassius auratus is one of the most important aquaculture species in China. The infection with C. auratus herpesvirus (CaHV) often causes 100% mortality. Tumor necrosis factor (TNF) and its receptors (TNFRs) are essential in host antiviral defense. However, viral homologs of TNFRs (vTNFRs) are encoded by viruses to carry out immune evasion. In this study, the functions of the two vTNFRs in CaHV (CaHV-vTNFRs), designated ORF144L and ORF146R, were firstly described. Molecular docking identified host TNF1 as a potential ligand for CaHV-vTNFRs, which was then experimentally validated by co-immunoprecipitation (Co-IP). Overexpression of CaHV-vtnfrs conferred a survival advantage on infected cells and promoted viral propagation in vitro, alongside the downregulation of host tnf1 and tnfr genes. The onset of apoptosis was delayed and inflammatory reactions were inhibited, as indicated by the expression of relevant genes (bax, bcl, il-1β, il-10, il-8, and tgf-β). Among these, CaHV-ORF146R exhibited a stronger immune evasion activity compared to CaHV-ORF144L. Our findings elucidate the function of vTNFRs in immune evasion and enhance our understanding of herpesvirus-host interactions. Furthermore, this work establishes a solid foundation for the development of targeted strategies to prevent and control future CaHV outbreaks.