African swine fever(ASF)is an acute,hemorrhagic,and highly contagious disease in pigs caused by the African swine fever virus(ASFV).Our previous studies have demonstrated that deletion of the MGF360-9L gene weakens AS...African swine fever(ASF)is an acute,hemorrhagic,and highly contagious disease in pigs caused by the African swine fever virus(ASFV).Our previous studies have demonstrated that deletion of the MGF360-9L gene weakens ASFV virulence in pigs,yet the underlying mechanism remains unclear.To investigate the mechanism of MGF360-9L regulating ASFV pathogenicity,the relationship between MGF360-9L and host proteins was identified by mass spectrometry.We found that host protein DEAD-box helicase 20(DDX20)interacted with and colocalized with MGF360-9L.Overexpression of DDX20 inhibited ASFV replication,whereas knockdown of DDX20 had the opposite effects.Moreover,DDX20 inhibited ASFV replication by promoting the activation of type I interferon signaling.Surprisingly,DDX20 was gradually degraded following ASFV infection.Mechanistically,MGF360-9L promoted the autophagic degradation of DDX20 by recruiting autophagy-related protein Ras-related protein Rab-1A(Rab1A).Silencing Rab1A suppressed ASFV replication,while overexpression of Rab1A exhibited the opposite effects.Furthermore,Rab1A,MGF360-9L and DDX20 could form a complex to facilitate the degradation of DDX20.Knockdown of Rab1A impaired MGF360-9L-mediated degradation of DDX20 during ASFV infection.In summary,our study demonstrates that MGF360-9L targets DDX20 for autophagy degradation to antagonize its antiviral function and facilitate ASFV replication.This finding broadens our understanding of the regulatory network between ASFV and its host,and provides new insights into the pathogenesis and immune evasion mechanisms of ASFV.展开更多
基金supported by the grants from the open competition program of top ten critical priorities of Agricultural Science and Technology Innovation for the 14th Five-Year Plan of Guangdong Province(2024KJ14)the Fundamental Research Funds for the Central Universities(lzujbky-2022-ct02)+7 种基金the Project of National Center of Technology Innovation for Pigs(NCTIP-XD/C03)the Youth Innovation Program of the Chinese Academy of Agricultural Sciences(Y2025QC33)the Major Science and Technology Project of Gansu Province(22ZD6NA001 and 22ZD6NA012)the Innovation Program of Chinese Academy of Agricultural Sciences(CAAS-CSLPDCP-2023002 and CAAS-ASTIP-2025-LVRI)the China Postdoctoral Science Foundation(2023M743830)the Earmarked Fund for CARS-35 and CARS-39-13he Fundamental Research Funds for Innovation Team of Gansu Province(23JRRA546,23JRRA548)the Basic Scientific Research Fund of LVRI(1610312021009).
文摘African swine fever(ASF)is an acute,hemorrhagic,and highly contagious disease in pigs caused by the African swine fever virus(ASFV).Our previous studies have demonstrated that deletion of the MGF360-9L gene weakens ASFV virulence in pigs,yet the underlying mechanism remains unclear.To investigate the mechanism of MGF360-9L regulating ASFV pathogenicity,the relationship between MGF360-9L and host proteins was identified by mass spectrometry.We found that host protein DEAD-box helicase 20(DDX20)interacted with and colocalized with MGF360-9L.Overexpression of DDX20 inhibited ASFV replication,whereas knockdown of DDX20 had the opposite effects.Moreover,DDX20 inhibited ASFV replication by promoting the activation of type I interferon signaling.Surprisingly,DDX20 was gradually degraded following ASFV infection.Mechanistically,MGF360-9L promoted the autophagic degradation of DDX20 by recruiting autophagy-related protein Ras-related protein Rab-1A(Rab1A).Silencing Rab1A suppressed ASFV replication,while overexpression of Rab1A exhibited the opposite effects.Furthermore,Rab1A,MGF360-9L and DDX20 could form a complex to facilitate the degradation of DDX20.Knockdown of Rab1A impaired MGF360-9L-mediated degradation of DDX20 during ASFV infection.In summary,our study demonstrates that MGF360-9L targets DDX20 for autophagy degradation to antagonize its antiviral function and facilitate ASFV replication.This finding broadens our understanding of the regulatory network between ASFV and its host,and provides new insights into the pathogenesis and immune evasion mechanisms of ASFV.
