High level expression of ISG12(1) promotes cell apoptosis via mitochondrial-dependent pathway and so as to hinder Newcastle disease virus replication

Newcastle disease (ND), caused by virulent Newcastle disease virus (NDV), poses a considerable risk for the poultry industry. A comprehensive understanding of the interaction between NDV and its host is therefore critical for control of this disease. Previously, we found that chicken ISG12(1) was among the significantly upregulated interferon-stimulated genes (ISGs) in embryos and the bursa of Fabricius of chickens infected by NDV, based on transcriptome sequencing. However, its antiviral effects and function were poorly understood. In this study, we aimed to determine the effects of chicken ISG12(1) on NDV replication. First, we confirmed that NDV infection stimulated high level expression of chicken ISG12(1) in vivo and in vitro based on RT-qPCR. Next, through overexpression and knockdown experiments, the antiviral activity of ISG12(1) was investigated. As expected, this protein was found to hinder NDV replication. In addition, we showed that ISG12(1) localized to the mitochondria; promoted the redistribution of Bax, a proapoptotic protein causing irreversible loss of mitochondria function, from the cytoplasm to the mitochondria; and therefore induced cell apoptosis. In conclusion, elucidation of the role of chicken ISG12(1) in combatting NDV infection contributes to our understanding of the responses of poultry to viruses and may facilitate the generation of more efficient vaccines to control ND.