Viral suppression of type I interferon signaling by NSs of DBV, SFSV and UUKV via NSs-mediated RIG-I degradation

Phenuiviridae, a member of theBunyavirales order, can lead to significant human morbidity and mortality. Various phenuiviruses target specific cellular proteins and have strategies to counteract the effects of type I interferon (IFN). Previous studies have shown that phenuiviruses infection inhibits the synthesis of type I IFNs, and viral nonstructural proteins (NSs) had been further identified as an IFN antagonist. This study found that the NSs proteins of Dabie bandavirus (DBV), Sandfly fever Sicilian virus (SFSV), and Uukuniemi virus (UUKV) can inhibit Sendai virus-induced activation of IFN-β promoter and phosphorylation of IFN regulatory factor 3 (IRF3). Moreover, detailed analysis revealed that the phenuivirus NSs protein could directly interact with retinoic acid inducible gene-I (RIG-I) and degrade it via a proteasome-dependent pathway. In short, this study demonstrate a novel mechanism of phenuiviruses to resist host antiviral immunity, which may help understand these pathogens and suggest novel therapeutic approaches.