The duck plague virus UL7 protein mediates RIG-I degradation to block host antiviral responses and promote viral pathogenesis.

Abstract

Duck plague (DP), which is caused by duck plague virus (DPV), is an acute, highly contagious disease with an extremely high mortality rate, and poses a serious threat to the waterfowl industry. DPV, which is an immunosuppressive virus, can significantly suppress host innate immune responses during the late stages of infection. However, the specific mechanisms by which the DPV UL7 protein functions in the viral replication cycle and immune evasion remain unclear. This study demonstrated that the DPV UL7 protein markedly inhibited IFN-β promoter activity, downregulated the transcription levels of IFN-β and downstream interferon-stimulated genes (ISGs), and suppressed the IFN-β promoter activity activated by effector molecules such as STING, cGAS, RIG-I, MDA5, MAVS, TBK1, and IRF7. Further research revealed that the UL7 protein directly interacted with RIG-I, inducing its degradation via the proteasome and lysosome pathways, thereby effectively inhibiting the host innate immune response. Although the UL7 protein was not involved in early infection processes such as viral adsorption, entry, or genome replication, it significantly promoted viral particle release and cell-to-cell spread, thereby increasing DPV proliferation in vitro. In vivo animal infection experiments further confirmed that compared with the parental virus DPV-CHv50 and the revertant virus DPV-UL7Rev, ducklings infected with the UL7 gene-deleted strain DPV-UL7presented significantly milder clinical symptoms, markedly reduced pathological damage in various organs, and a substantial decrease in mortality. These findings not only elucidate the molecular mechanism by which the UL7 protein mediates immune evasion by targeting RIG-I but also highlight its critical role in the pathogenicity of DPV.