Neddylation Facilitates White Spot Syndrome Virus Replication In Marsupenaeus Japonicus Through Mediating Dorsal Translocation

Neddylation is a kind of Ubiquitination like post-translational modification that adds small modifier Nedd8 which is most close to Ubiquitin to specific protein substrates through E1,the activating enzyme,E2,the conjugating enzyme and E3,the ligase.Both neddylation and ubiquitination pathways are closely correlated with innate immunity.However,the detail mechanism of the pathway in innate immunity is not clear.In our research,all three enzyme genes encoding Els(heterodimer of APPBP1 and UBA3),E2s(UBC12-1 and UBC12-2)and E3s(RBX1,RBX2 and DCN)in Neddylation pathway were identified in Kuruma shrimp,Marupenaeus japonicus.They all were upregulated post white spot syndrome virus(WSSV)challenge in shrimp.This result indicated that Neddylation pathway was involved in WSSV infection in shrimp.Then,we found that Neddylation pathway was beneficial for WSSV replication in shrimp through MLN4924 injection,an inhibitor of E1 avtivity.After knockdown of the El(APPBP1 and UBA3),E2(UBC12-1 and UBC12-2)and E3(RBX1 and DCN),same results were obtained with MLN4924 injection.Further study found that after injection of MLN4924,Dorsal translocation into nucleus was inhibited and transcription of antimicrobial peptides(including Cru I-1,Cru I-3,ALF-B1 and ALF-C2)regulated by Dorsal was also declined.These results suggested that Neddylation pathway promoted Dorsal translocation.There are several reports revealed that Dorsal translocation promoted transcription of immediate early gene 1(ie1)of WSSV and was beneficial for WSSV duplication.Therefore,our results suggested that neddylation pathway mediated Dorsal translocation and promote WSSV replication in shrimp..