ISG15 inhibits replication of type Ⅱ grass carp reovirus (GCRV-II) by degrading viral NS79 and VP41 proteins

In response to viral infection, ISGs are induced to act as antiviral factors. However, which ISGs are induced upon GCRV-II infection and function as anti-GCRV-II factors remains largely unknown. In this study, we analyzed transcriptomic data from grass carp kidneys with or without GCRV-Ⅱ infection and identified nine ISGs in response to GCRV-Ⅱ infection including ISG15-1 and ISG15-2. ISG15-1 and ISG15-2 inhibited GCRV-II replication via degradation of NS79 and VP41 proteins of GCRV-II through the autophagy-lysosomal pathway. Moreover, GCRV-II utilized NS38 to rescue the degradation of VP41 by disrupting the ISG15s-VP41 interaction through competitively binding to ISG15s, thus achieving immune evasion.