Ring-finger protein 34 facilitates nervous necrosis virus evading antiviral innate immunity by targeting TBK1 and IRF3 for ubiquitination and degradation

Ubiquitination enables a tight control on host immune responses, and could be hijacked by viruses for their survival. Here, we found fish pathogen nervous necrosis virus (NNV) recruited an E3 ubiquitin ligase ring finger protein 34 (RNF34) to inhibit RLRs-mediated interferons (IFN) response via ubiquitinating TBK1 and IRF3. RNF34 was found greatly enhanced NNV replication and prevented IFN production. Mechanically, RNF34 targeted TBK1 and IRF3 of different fish species for K27 and K48-linked ubiquitination degradation, which in turn diminishing TBK1-induced translocation of IRF3 from cytoplasm to nucleus. Furthermore, NNV capsid protein (CP) directly bind with different fishes RNF34, and CP-induced TBK1 and IRF3 degradation and IFN suppression depended on RNF34. Our findings demonstrated a novel mechanism by which NNV CP evaded host innate immunity via RNF34, and provided a potential drug target for the control of NNV infection. ### Competing Interest Statement The authors have declared no competing interest.