Inhibition of cGAS-STING-TBK1 signaling pathway by DP96R of ASFV China 2018/1

ASFV; DP96R; NF-κB; TBK1; Type I IFN; DP96R protein; I kappa B kinase beta; STING protein; TBK1 protein; MB21D1 protein, human; MPYS protein, human; TBK1 protein, human; African swine fever virus; Article; HEK293 cell line; Animals; Genes, Viral; HEK293 Cells; Humans; Interferon-beta; Membrane Proteins; NF-kappa B; Nucleotidyltransferases; Phosphorylation; Protein Domains; Protein-Serine-Threonine Kinases; Signal Transduction; Viral Proteins

Abstract :

[en] African swine fever virus (ASFV) is a highly pathogenic large DNA virus that causes African swine fever (ASF) in domestic pigs and European wild boars with mortality rate up to 100%. The DP96R gene of ASFV encodes one of the viral virulence factors, yet its action mechanism remains unknown. In this study, we report that DP96R of ASFV China 2018/1 strain subverts type I IFN production in cGAS sensing pathway. DP96R inhibited the cGAS/STING, and TBK1 but not IRF3-5D mediated IFN-β and ISRE promoters activation. Furthermore, DP96R selectively blocked the activation of NF-κB promoter induced by cGAS/STING, TBK1, and IKKβ, but not by overexpression of p65. Moreover, DP96R inhibited phosphorylation of TBK1 stimulated by cGAS/STING activation, and TBK1-induced antiviral response. Finally, truncated mutation analysis demonstrated that the region spanning amino acids 30 to 96 of DP96R was responsible for the inhibitory activity. To our knowledge, this is for the first time that DP96R of ASFV China 2018/1 is reported to negatively regulate type I IFN expression and NF-κB signaling by inhibiting both TBK1 and IKKβ, which plays an important role in virus immune evasion. © 2018 Elsevier Inc.

Disciplines :

Veterinary medicine & animal health

Author, co-author :

Wang, X.; Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China

Wu, Jing ; Université de Liège - ULiège

Wu, Y.; Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China

Chen, H.; Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, China

Zhang, S.; Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, 130000, China

Li, J.; Chinese Academy of Agricultural Sciences, Beijing, 100081, China

Xin, T.; Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China

Jia, H.; Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China

Hou, S.; Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China

Jiang, Y.; Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China

Zhu, H.; Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China

Guo, X.; Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China

Language :

English

Title :

Inhibition of cGAS-STING-TBK1 signaling pathway by DP96R of ASFV China 2018/1

Publication date :

2018

Journal title :

Biochemical and Biophysical Research Communications

ISSN :

0006-291X

eISSN :

1090-2104

Publisher :

Elsevier, Atlanta, United States - California

Volume :

506

Issue :

Pages :

437-443

Peer reviewed :

Peer reviewed

Available on ORBi :

since 18 December 2021

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