The Nucleoprotein and Phosphoprotein of Peste des Petits Ruminants Virus Inhibit Interferons Signaling by Blocking the JAK-STAT Pathway
| Autor: | Xiangle Zhang, Li Linlin, Dang Wen, Xiaoli Du, Miaotao Zhang, Haixue Zheng, Pengfei Li, Chunyan Wu, Qinghong Xue, Xiangtao Liu, Yuchen Nan, Zixiang Zhu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Response element lcsh:QR1-502 Virus Replication lcsh:Microbiology Article Peste-des-petits-ruminants virus 03 medical and health sciences Interferon-gamma Interferon Virology Peste-des-Petits-Ruminants medicine Animals Humans STAT1 STAT2 peste des petits ruminants virus nucleoprotein Janus Kinases Innate immune system 030102 biochemistry & molecular biology biology fungi JAK-STAT signaling pathway food and beverages interferon Interferon-beta Nucleocapsid Proteins phosphoprotein Phosphoproteins JAK/STAT Immunity Innate Cell biology 030104 developmental biology HEK293 Cells Nucleoproteins STAT1 Transcription Factor Infectious Diseases Host-Pathogen Interactions biology.protein Phosphorylation Interferons Signal transduction medicine.drug Signal Transduction |
| Zdroj: | Viruses Viruses, Vol 11, Iss 7, p 629 (2019) Volume 11 Issue 7 |
| ISSN: | 1999-4915 |
| DOI: | 10.3390/v11070629 |
| Popis: | 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-&beta 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-&beta and IFN-&gamma induced activation of IFN-stimulated response element (ISRE) and IFN-&gamma activated site (GAS) element, respectively. Both N and P proteins, functioning as novel IFN response antagonists, markedly suppressed IFN-&beta induced ISRE and IFN-&gamma 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |