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
目的探讨SAMD9L在弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)中的表达及临床意义。方法采用免疫组化EnVision法检测135例DLBCL中SAMD9L的表达,分析SAMD9L表达与DLBCL临床病理特征、治疗反应及总生存期(overall survival,...目的探讨SAMD9L在弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)中的表达及临床意义。方法采用免疫组化EnVision法检测135例DLBCL中SAMD9L的表达,分析SAMD9L表达与DLBCL临床病理特征、治疗反应及总生存期(overall survival,OS)之间的相关性。结果SAMD9L表达与患者年龄(P=0.049)、B症状(P=0.003)、国际预后指数(international prognostic index,IPI)评分(P=0.026)相关,其在年龄>60岁、有B症状以及高IPI评分患者中表达较高。但SAMD9L低表达组和高表达组患者在性别、结外累及、Hans分型、Ann Arbor分期、美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)体能状态(performances status,PS)评分、Ki-67增殖指数、骨髓浸润、乳酸脱氢酶(lactate dehydrogenase,LDH)水平、白蛋白(albumin,ALB)水平以及治疗反应方面差异无显著性(P均>0.05)。Kaplan-Meier生存曲线分析显示,SAMD9L高表达组较低表达组的OS显著缩短(P<0.001)。单因素和多因素回归分析显示,SAMD9L表达水平是影响OS的相关因素,但非预后的独立影响因素(P=0.710)。结论SAMD9L在患者年龄>60岁、有B症状以及高IPI评分患者中表达较高。SAMD9L高表达组较低表达组的OS显著缩短,SAMD9L表达水平是影响DLBCL患者OS的相关因素,但非预后的独立影响因素。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.
