Investigating E3 ubiquitin ligase activity of ORF150 in fish herpesvirus pathogenesis

Fish herpesviruses, members of the family Alloherpesviridae , infect aquatic species. The host’s ubiquitin-proteasome system (UPS) serves as the major intracellular pathway for protein degradation and plays a crucial role in the viral replication cycle. Viruses exploit the UPS to facilitate their replication and evade host immune responses. This study demonstrated that cyprinid herpesvirus 2 (CyHV-2) infection significantly activates the host UPS pathway, as revealed by transcriptomics sequencing analysis. Further, treatment with MG132, a proteasome inhibitor, markedly downregulates intracellular viral replication and gene transcription. Additionally, we identified a novel, highly conserved E3 ubiquitin ligase with a C3HC4-type really interesting gene (RING)-finger (RING-HC) domain, encoded by open reading frame 150 ( ORF150 ) of CyHV-2. These findings provide critical molecular evidence that the host UPS is essential for fish herpesvirus replication and suggest that viral E3 ligases may serve as potential targets for new antiviral strategies.