African swine fever virus MGF505-7R protein interacted with IRF7and TBK1 to inhibit type I interferon production

Kaidian Yang; Ying Xue; Tianming Niu; Xinyang Li; Mingyang Cheng; Meiying Bao; Boshi Zou; Chunwei Shi; Jianzhong Wang; Wentao Yang; Nan Wang; Yanlong Jiang; Guilian Yang; Yan Zeng; Xin Cao; Chunfeng Wang

doi:10.1016/j.virusres.2022.198931

African swine fever virus MGF505-7R protein interacted with IRF7and TBK1 to inhibit type I interferon production

Virus Res. 2022 Dec:322:198931. doi: 10.1016/j.virusres.2022.198931. Epub 2022 Sep 18.

Authors

Affiliations

¹ College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, China.
² College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, China. Electronic address: zengyan@jlau.edu.cn.
³ College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, China. Electronic address: xinc@jlau.edu.cn.
⁴ College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, China. Electronic address: wangchunfeng@jlau.edu.cn.

PMID: 36130654
DOI: 10.1016/j.virusres.2022.198931

Abstract

African swine fever virus (ASFV) employs diverse strategies to confront or evade host type I interferon (IFN-I)-induced antiviral responses. Moreover, the mechanisms of this process are largely unknown. Here, we assessed 27 ASFV proteins to determine whether any of them suppressed the cGAS-STING pathway to facilitate immune evasion. Using dual-luciferase assays, we found that ASFV MGF505-7R suppressed the activity of the IFN-β and ISRE promoters and the expression of IFN-I and ISGs. MGF505-7R interacted with IRF7 and TBK1, degrading IRF7 by autophagy, cysteine, and proteasome pathways and TBK1 by the proteasome pathway. Moreover, TBK1 and IRF3 were phosphorylated by cGAS-STING stimulation. Finally, small interfering RNA (siRNA)-based silencing of MGF505-7R enhanced IFN-I antiviral activity. Taken together, these results preliminarily clarified the immune escape mechanism of ASFV MGF505-7R, which provides a potential target for developing antiviral agents.

Keywords: African swine fever virus; IRF7; Interferon; MGF505-7R; TBK1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

African Swine Fever Virus* / genetics
African Swine Fever*
Animals
Antiviral Agents / metabolism
Antiviral Agents / pharmacology
Interferon Type I*
Nucleotidyltransferases / metabolism
Proteasome Endopeptidase Complex / metabolism
Swine
Viral Proteins / genetics
Viral Proteins / metabolism

Substances

Proteasome Endopeptidase Complex
Viral Proteins
Nucleotidyltransferases
Interferon Type I
Antiviral Agents