Zebrafish Maoc1 Attenuates SVCV Propagation By Promoting Autophagy-lysosome-dependent Degradation Of Viral Phosphoprotein

In the process of aquaculture,diseases caused by viral infections have always been an important issue affecting the production of farmed fish,it has the characteristics of short course,concentrated outbreak and high fatality rate.The spring viremia of carp(SVC)caused by the spring viremia of carp virus(SVCV)is a viral disease that results in massive death of farmed carp fish.Studying the mechanism of host infection by SVCV,the way in which it interacts with host proteins to achieve immune evasion,and the strategies that hosts use to resist SVCV are all of great significance for understanding the pathogenesis of SVCV and guiding disease prevention and control.Although fish have innate immune system and adaptive immune system to resist pathogen infection,there have been few reports on how hosts directly resist virus proliferation after SVCV infection,and its molecular mechanism is still unclear.In this study,we identified a new gene,called maoc1,which was significantly induced by SVCV infection.First,using CRISPR/Cas9 technology,we successfully constructed a zebrafish strain with maoc1 deletion.We found that compared with wild-type zebrafish,the maoc1-deficient zebrafish were more susceptible to SVCV infection,with significantly reduced survival rates,while their internal virus replication and of antiviral genes were significantly increased.Further studies showed that maoc1 interacted with SVCV phosphoprotein and degraded it through the autophagy-lysosome pathway,thereby limiting SVCV proliferation.These findings reveal the unique defense mechanism of zebrafish against SVCV infection.The SVCV phosphoprotein plays an important role in virus replication and immune evasion.This study found that maoc1 inhibits SVCV replication by directly binding and promoting the degradation of phosphoprotein through the autophagy-lysosome pathway,demonstrating that maoc1 is a novel gene induced by SVCV and has antiviral ability.Therefore,this study not only revealed the important role of maoc1 in combating SVCV infection,but also demonstrated a unique host defense mechanism against viral invasion.