ISG20 inhibits bluetongue virus replication

ISG20 is an interferon-inducible exonuclease that inhibits virus replication. Although ISG20 is thought to degrade viral RNA, the antiviral mechanism and specificity of ISG20 remain unclear. In this study, the antiviral role of ovine ISG20(o ISG20) in bluetongue virus(BTV) infection was investigated. It was found that BTV infection upregulated the transcription of ovine ISG20(o ISG20) in a time-and BTV multiplicity of infection(MOI)-dependent manner. Overexpression of o ISG20 suppressed the production of BTV genome, proteins, and virus titer, whereas the knockdown of o ISG20 increased viral replication. o ISG20 was found to co-localize with BTV proteins VP4,VP5, VP6, and NS2, but only directly interacted with VP4. Exonuclease defective o ISG20 significantly decreased the inhibitory effect on BTV replication. In addition, the interaction of mutant o ISG20 and VP4 was weakened,suggesting that binding to VP4 was associated with the inhibition of BTV replication. The present data characterized the anti-BTV effect of o ISG20, and provides a novel clue for further exploring the inhibition mechanism of double-stranded RNA virus by ISG20.