The Effects of Bovine Viral Diarrhoea Virus(BVDV)-induced Ferroptosis on Virus Replication
This study aimed to investigate the regulatory effect of bovine viral diarrhoea virus(BVDV)infection on ferroptosis in Madin-Darby Bovine Kidney(MDBK)cells and its effect on viral replication.Technologies such as confocal microscopy,Western blot,qPCR and electron microscopy were used to detect ferroptosis and the level of viral replication in BVDV-infected cells.Furthermore,the viral replication level and inflammatory cytokines expression in BVDV-infected cells pretreated with Fer-1,a commonly used ferroptosis inhibitor,were also detected.The results showed that,compared with the normal control group,the mortality rate of cells in-fected with BVDV(MOI=5)was significantly increased(P<0.05),which was accompanied with increased levels of Fe2+and lipid peroxidation(P<0.05).Transmission electron microsco-py(TEM)analysis revealed that BVDV-infected and Erastin-treated cells displayed shrunk mito-chondria with fewer cristae,increased mitochondrial membrane density and decreased mitochon-drial mean areas compared with those of mock-infected cells,which was a typical morphological feature of ferroptosis.Fer-1 treatment significantly inhibited the levels of viral replication in BVDV-infected cells(P<0.05).In addition,ferroptosis induced by BVDV infection had positive regulatory effects on inflammatory cytokines expression,including IL-1β,IL-18 and IFN-β.The results suggested that BVDV infection can induce ferroptosis in host cells,and the induction of ferroptosis enhanced the level of viral replication and the expression of inflammatory cytokines.