Bluetongue virus non-structural protein 3 (NS3) and NS4 coordinatively antagonize type Ⅰ interferon signaling by targeting STAT1.

Zhuoran Li, Danfeng Lu, Heng Yang, Zhuoyue Li, Pei Zhu, Jiarui Xie, Defang Liao, Yongtang Zheng, Huachun Li

Veterinary microbiology 2021 Mar

filter terms:

Previous studies have pointed out that bluetongue virus (BTV) down-regulates the expression levels of type Ⅰ interferon (IFN-Ⅰ) and inhibits IFN-Ⅰ signaling by targeting on the Janus tyrosine kinase (JAK)-signal transducer and activator of transcription protein (STAT) pathway. However, individual viral protein could not effectively block IFN-Ⅰ signaling. There is a need to explore the underlying mechanisms by which viral proteins of BTV coordinate to antagonize the IFN-Ⅰ signaling. We investigated the coordinative role of BTV-1 nonstructural protein 3 (NS3) and NS4 in counteracting IFN-Ⅰ signaling in the JAK-STAT pathway by directly interacting with STAT1. The NS3 and NS4 targeted the SH2 domain of STAT1 to inhibit its phosphorylation, heterodimerization, nuclear translocation, as well as activation of downstream genes of the JAK-STAT pathway. NS3 and NS4 impaired STAT1 phosphorylation induced by IFN-Ⅰ in a dose dependent manner. Overall, this study confirmed that NS3 and NS4 of BTV participate in interfering with IFN-Ⅰ signaling process. Also, a new mechanism employed by BTV to evade host innate immune responses was revealed. Copyright © 2021 Elsevier B.V. All rights reserved.

Citation

Zhuoran Li, Danfeng Lu, Heng Yang, Zhuoyue Li, Pei Zhu, Jiarui Xie, Defang Liao, Yongtang Zheng, Huachun Li. Bluetongue virus non-structural protein 3 (NS3) and NS4 coordinatively antagonize type Ⅰ interferon signaling by targeting STAT1. Veterinary microbiology. 2021 Mar;254:108986