African Swine Fever Virus MGF360-12L Inhibits Type Ⅰ Interferon Production by Blocking the Interaction of Importin α and NF-κB Signaling Pathway

African swine fever(ASF)is an infectious transboundary disease of domestic pigs and wild boar and spreading throughout Eurasia.There is no vaccine and treatment available.Complex immune escape strategies of African swine fever virus(ASFV)are crucial factors affecting immune prevention and vaccine development.MGF360 genes have been implicated in the modulation of the IFN-Ⅰresponse.The molecular mechanisms contributing to innate immunity are poorly understood.In this study,we demonstrated that ASFV MGF360-12 L(MGF360 families 12 L protein)significantly inhibited the mRNA transcription and promoter activity of IFN-βand NF-κB,accompanied by decreases of IRF3,STING,TBK1,ISG54,ISG56 and AP-1 m RNA transcription.Also,MGF360-12 L might suppress the nuclear localization of p50 and p65 mediated by classical nuclear localization signal(NLS).Additionally,MGF360-12 L could interact with KPNA2,KPNA3,and KPNA4,which interrupted the interaction between p65 and KPNA2,KPNA3,KPNA4.We further found that MGF360-12 L could interfere with the NF-κB nuclear translocation by competitively inhibiting the interaction between NF-κB and nuclear transport proteins.These findings suggested that MGF360-12 L could inhibit the IFN-Ⅰproduction by blocking the interaction of importinαand NF-κB signaling pathway,which might reveal a novel strategy for ASFV to escape the host innate immune response.