The Nucleoprotein and Phosphoprotein of Peste des Petits Ruminants Virus Inhibit Interferons Signaling by Blocking the JAK-STAT Pathway
Pengfei Li 1,2,†
, Zixiang Zhu 2,†, Xiangle Zhang 2, Wen Dang 2, Linlin Li 2, Xiaoli Du 2, Miaotao Zhang 1, Chunyan Wu 1, Qinghong Xue 3, Xiangtao Liu 2, Haixue Zheng 2,* and Yuchen Nan 1,*
, Zixiang Zhu 2,†, Xiangle Zhang 2, Wen Dang 2, Linlin Li 2, Xiaoli Du 2, Miaotao Zhang 1, Chunyan Wu 1, Qinghong Xue 3, Xiangtao Liu 2, Haixue Zheng 2,* and Yuchen Nan 1,*
1
Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China
2
State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
3
China Institute of Veterinary Drug Control, Beijing100081, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Viruses 2019, 11(7), 629; https://doi.org/10.3390/v11070629
Received: 17 June 2019 / Revised: 3 July 2019 / Accepted: 6 July 2019 / Published: 8 July 2019
(This article belongs to the Section Animal Viruses)
Abstract
Peste des petits ruminants virus (PPRV) is associated with global peste des petits ruminants resulting in severe economic loss. Peste des petits ruminants virus dampens host interferon-based signaling pathways through multiple mechanisms. Previous studies deciphered the role of V and C in abrogating IFN-β production. Moreover, V protein directly interacted with signal transducers and activators of transcription 1 (STAT1) and STAT2 resulting in the impairment of host IFN responses. In our present study, PPRV infection inhibited both IFN-β- and IFN-γ-induced activation of IFN-stimulated response element (ISRE) and IFN-γ-activated site (GAS) element, respectively. Both N and P proteins, functioning as novel IFN response antagonists, markedly suppressed IFN-β-induced ISRE and IFN-γ-induced GAS promoter activation to impair downstream upregulation of various interferon-stimulated genes (ISGs) and prevent STAT1 nuclear translocation. Specifically, P protein interacted with STAT1 and subsequently inhibited STAT1 phosphorylation, whereas N protein neither interacted with STAT1 nor inhibited STAT1 phosphorylation as well as dimerization, suggesting that the N and P protein antagonistic effects were different. Though they differed in their relationship to STAT1, both proteins blocked JAK-STAT signaling, severely negating the host antiviral immune response. Our study revealed a new mechanism employed by PPRV to evade host innate immune response, providing a platform to study the interaction of paramyxoviruses and host response. View Full-Text
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Li, P.; Zhu, Z.; Zhang, X.; Dang, W.; Li, L.; Du, X.; Zhang, M.; Wu, C.; Xue, Q.; Liu, X.; Zheng, H.; Nan, Y. The Nucleoprotein and Phosphoprotein of Peste des Petits Ruminants Virus Inhibit Interferons Signaling by Blocking the JAK-STAT Pathway. Viruses 2019, 11, 629.
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