African swine fever virus MGF360-9L degrades DDX20 through the Rab1A-dependent autophagy pathway to antagonize its antiviral effect

Lu He; Xuxu Fan; Zhaoyu Zhu; Danshi Pei; Yizhuo Wang; Xizhong Li; Qingfeng Ren; Haixue Zheng; Weiwei Li; Zixiang Zhu

doi:10.1016/j.virs.2025.10.001

October 2025

Citation: Lu He, Xuxu Fan, Zhaoyu Zhu, Danshi Pei, Yizhuo Wang, Xizhong Li, Qingfeng Ren, Haixue Zheng, Weiwei Li, Zixiang Zhu. African swine fever virus MGF360-9L degrades DDX20 through the Rab1A-dependent autophagy pathway to antagonize its antiviral effect .VIROLOGICA SINICA, 2025, 40(5) : 822-834. http://dx.doi.org/10.1016/j.virs.2025.10.001

African swine fever virus MGF360-9L degrades DDX20 through the Rab1A-dependent autophagy pathway to antagonize its antiviral effect

Lu He ^a,b,c ,
Xuxu Fan ^a,b,c ,
Zhaoyu Zhu ^a,b,c ,
Danshi Pei ^a,b,c ,
Yizhuo Wang ^a,b,c ,
Xizhong Li ^a,b,c ,
Qingfeng Ren ^a,b,c ,
Haixue Zheng ^{a,b,c
,,} ,
Weiwei Li ^{a,b,c
,,} ,
Zixiang Zhu ^{a,b,c
,,}

a. State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730000, China;
b. African Swine Fever Regional Laboratory of China, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China;
c. Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou 730046, China

Corresponding author: Haixue Zheng, haixuezheng@163.com
Weiwei Li, liweiwei@caas.cn
Zixiang Zhu, zhuzixiang@caas.cn
Received Date: 15 April 2025
Accepted Date: 13 October 2025
Available online: 14 October 2025

Abstract

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.
- African swine fever virus (ASFV)
- , MGF360-9L
- , DDX20
- , Rab1A
- , Protein degradation
- , Autophagy

Electronic Supplementary Material

10.1016j.virs.2025.10.001-ESM1.docx
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