Inhibition of rabies virus replication by interferon-stimulated gene 15 and its activating enzyme UBA7

It was reported that ISG15 and its activating enzyme UBA7 have antiviral functions. However, there is no study to demonstrate whether ISG15 and UBA7 have anti-rabies virus function. In the current study, In vivo and in vitro anti-rabies virus function of ISG15 and UBA7 were investigated using RNAi technology. The results showed that shRNA knock-down of expression of ISG15 and UBA7 increased the titers of RABV in neuroblastoma cell line NA and microglial cell line BV-2 cells and shRNA knockdown of ISG15 conjugation alleviates the IFN-induced inhibition of RABV gene expression in vitro. Lentiviral vector mediated-shRNA knock-down of expression of ISG15 and UBA7 increased the titers of RABV in mouse brains and decreased the survivorship of mice. The study showed that ISG15 and UBA7 inhibit RABV replication in vitro and in vivo. To our knowledge, we for the first time documented the anti-RABV function of ISG15 and UBA7, which may provide a means of understanding the pathogenesis of rabies and improving therapeutic methods.