STAU1 binds to IBDV genomic double-stranded RNA and promotes viral replication via attenuation of MDA5-dependent b interferon induction

Infectious bursal disease virus (IBDV)infection triggers the induction of type I IFN,whichismediatedby melanoma differentiation-associated protein 5 recognition of the viral genomic double-stranded RNA (dsRNA). However, themechanismof IBDVovercoming the type I IFNantiviral response remains poorly characterized.Here, weshowthat IBDVgenomicdsRNAselectivelybinds to thehost cellularRNAbindingproteinStaufen1 (STAU1) in vitro and in vivo.The viraldsRNAbinding regionwasmapped to theN-terminalmoiety ofSTAU1 (residues 1-468). Down-regulation of STAU1 impaired IBDV replication and enhanced IFN-b transcription in response to IBDV infection, while having little effect on the viral attachment to the host cells and cellular entry. Conversely, overexpression of STAU1 but not the IBDV dsRNA-binding deficient STAU1 mutant (469-702) led to a suppression of IBDV dsRNA-induced IFN-b promoter activity.Moreover, we found that the binding of STAU1 to IBDV dsRNA decreased the association of melanoma differentiation-associated protein 5 but not VP3 with the IBDV dsRNA in vitro. Finally,we showed that STAU1 and VP3 suppressed IFN-b gene transcription in response to IBDV infection in an additive manner.Collectively, these findings provide a novel insight into the evasive strategies used by IBDV to escape the host IFNantiviral response.