Duck Tembusu Virus Nonstructural Protein 1 Antagonizes IFN-β Signaling Pathways by Targeting VISA.
Duck Tembusu virus (DTMUV) is an emergent infectious pathogen that has caused severe disease in ducks and huge economic losses to the poultry industry in China since 2009. Previously, we showed that DTMUV inhibits IFN-β induction early in infection; however, the mechanisms of the inhibition of innate immune responses remain poorly understood. In this study, we screened DTMUV-encoded structural and nonstructural proteins using reporter assays and found that DTMUV NS1 markedly suppressed virus-triggered IFN-β expression by inhibiting retinoic acid-inducible gene I-like receptor signaling. Moreover, we found that DTMUV NS1 specifically interacted with the C-terminal domain of virus-induced signaling adaptor and impaired the association of retinoic acid-inducible gene I or melanoma differentiation-associated gene 5 and virus-induced signaling adaptor, thereby downregulating the retinoic acid-inducible gene I-like receptor-mediated signal transduction and cellular antiviral responses, leading to evasion of the innate immune response. Together, our findings reveal a novel mechanism manipulated by DTMUV to circumvent the host antiviral immune response.
State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, People's Republic of China.
Junyong
J
Wang
College of Life Sciences, Medical Research Institute, Wuhan University, Wuhan 430072, People's Republic of China; zhuqiyun@caas.cn caoqilei@whu.edu.cn.
Cao-Qi
0000-0002-6142-4697
CQ
Lei
State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, People's Republic of China.
Yanhong
Y
Ji
State Key Laboratory of Agriculture Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Hongbo
H
Zhou
College of Life Sciences, Medical Research Institute, Wuhan University, Wuhan 430072, People's Republic of China.
Yujie
Y
Ren
State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, People's Republic of China.
Qianqian
Q
Peng
State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, People's Republic of China.
Yan
Y
Zeng
State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, People's Republic of China.
Yane
Y
Jia
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, People's Republic of China; and.
Jinying
J
Ge
College of Life Sciences, Medical Research Institute, Wuhan University, Wuhan 430072, People's Republic of China.
Bo
B
Zhong
College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, People's Republic of China.
Yu
Y
Li
College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, People's Republic of China.
Jianzhong
J
Wei
College of Life Sciences, Medical Research Institute, Wuhan University, Wuhan 430072, People's Republic of China.
Hong-Bing
HB
Shu
State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, People's Republic of China; zhuqiyun@caas.cn caoqilei@whu.edu.cn.
Qiyun
Q
Zhu
D000818:Animals; D030161:Avian Proteins / Q000378:metabolism*; D001715:Bird Diseases / Q000276:immunology*; D002681:China; D000071457:DEAD Box Protein 58 / Q000378:metabolism; D004372:Ducks / Q000276:immunology*; D005416:Flavivirus / Q000276:immunology*; D018177:Flavivirus Infections / Q000276:immunology*; D057131:Immune Evasion; D007111:Immunity, Cellular; D007113:Immunity, Innate; D000072640:Interferon-Induced Helicase, IFIH1 / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism*; D015398:Signal Transduction; D017361:Viral Nonstructural Proteins / Q000276:immunology*
D030161:Avian Proteins; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta; D000071457:DEAD Box Protein 58; D000072640:Interferon-Induced Helicase, IFIH1