Interferon-stimulated gene 15 facilitates BTV replication through interacting with the NS1 protein

Bluetongue virus (BTV) infection effectively activates the innate immune response, followed by expression of interferon (IFN) and multiple interferon-stimulated genes (ISGs). ISG15 is one most induced ISGs, often plays a role in inhibiting replication. This study aims to explore specific mechanisms ovine (oISG15) BTV infection. We found that transcription level oISG15 was upregulated time-dependent multiplicity infection-dependent manner. The overexpression exogenous enhances replication, whereas knockdown endogenous inhibits viral protein wild-type oISG15-overexpressed cells ISGylation defective have no significant differences, which indicated promoted replication an ISGylation-independent A co-immunoprecipitation assay showed four proteins—VP3, VP4, VP5, NS1—interacted with oISG15. also VP4 NS1 proteins associated ubiquitin via co-immunoprecipitation, improved stability both proteins. Further results degradation involved lysine 63-linked polyubiquitin. suggested may interfere autophagy pathway. provides new insights on interaction between ISG15, enriches our understanding regulation biological function