Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
      • Neuroimmunology: To Sense and Protect
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons

User menu

  • Subscribe
  • Log in

Search

  • Advanced search
The Journal of Immunology
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons
  • Subscribe
  • Log in
The Journal of Immunology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Follow The Journal of Immunology on Twitter
  • Follow The Journal of Immunology on RSS

Dysregulation of the RIG-I–like Receptor Pathway Signaling by Peste des Petits Ruminants Virus Phosphoprotein

Pengfei Li, Zixiang Zhu, Weijun Cao, Fan Yang, Xusheng Ma, Hong Tian, Keshan Zhang, Xiangtao Liu and Haixue Zheng
J Immunol February 1, 2021, 206 (3) 566-579; DOI: https://doi.org/10.4049/jimmunol.2000432
Pengfei Li
*State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zixiang Zhu
*State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Weijun Cao
*State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fan Yang
*State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xusheng Ma
*State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hong Tian
*State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Keshan Zhang
*State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiangtao Liu
*State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China; and
†National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Haixue Zheng
*State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF
Loading

Key Points

  • PPRV P protein inhibits type I IFN production.

  • PPRV P protein interacts with IRF3 to block the interaction between TBK1 and IRF3.

  • The 1–102 region of P protein is critical for the antagonistic function of P protein.

Visual Abstract

Figure1
  • Download figure
  • Open in new tab
  • Download powerpoint

Abstract

Peste des petits ruminants virus (PPRV) is a Morbillivirus that causes highly contagious and severe disease in various ruminants. PPRV infection leads to a severe inhibition of host antiviral immune response. Our previous study demonstrated that PPRV V protein blocks IFN response by targeting STAT proteins. In the current study, we identified the phosphoprotein (P) as a novel antagonistic factor of PPRV to counteract host antiviral innate immune response. PPRV P protein significantly suppressed RIG-I–like receptor pathway signaling and impaired IFN-β and ISGs expression by targeting IFN regulatory factor (IRF)3 in both human embryonic kidney 293T cells and primary goat fibroblasts. The 1–102 region of P protein was critical for the antagonistic function of P protein. P protein interacted with IRF association domain (IAD) of IRF3 to block the interaction between TBK1 and IRF3. The interaction between TBK1 and the IAD of IRF3 is responsible for triggering the phosphorylation of IRF3. P protein competed with TBK1 to bind to the IAD of IRF3 that contributed to the decreased phosphorylation of IRF3, which, in turn, interfered with the dimerization of IRF3 and blocked IRF3 nuclear transportation. Besides, we also found that P protein interacted with IRF5 and IRF8. However, the involved mechanism remains unknown. Taken together, our results reveal a novel mechanism by which PPRV P protein antagonizes host antiviral innate immune response by interacting with the transcription factor IRF3, thereby inhibiting the type I IFN production and promoting viral replication.

Footnotes

  • This work was supported by grants from the National Key Research and Development Program of China (2016YFE0204100), the Key Technologies Research and Development Program of Gansu Province (19ZDNA001), the Key Development and Research Foundation of Yunnan (2018BB004), and the Chinese Academy of Agricultural Science and Technology Innovation Project (CAAS-ASTIP-2020-LVRI).

  • The online version of this article contains supplemental material.

  • Abbreviations used in this article:

    CDV
    canine distemper virus
    coIP
    coimmunoprecipitation
    HA
    hemagglutinin
    HEK293T
    human embryonic kidney 293T cell line
    hpt
    hour posttransfection
    IAD
    IRF association domain
    IFA
    immunofluorescence assay
    IRF
    IFN regulatory factor
    ISG
    IFN-stimulated gene
    ISRE
    IFN-stimulated response element
    L
    polymerase
    M
    matrix
    MeV
    measles virus
    MOI
    multiplicity of infection
    N
    nucleocapsid
    NC siRNA
    negative control siRNA
    P
    phosphoprotein
    PAM
    pulmonary alveolar macrophage
    PPR
    peste des petits ruminants
    PPRV
    PPR virus
    qPCR
    real-time quantitative PCR
    RIG-I
    retinoic acid–inducible gene-I
    RLR
    RIG-I–like receptor
    RPV
    Rinderpest virus
    SeV
    Sendai virus
    siRNA
    small interfering RNA.

  • Received April 21, 2020.
  • Accepted November 15, 2020.
  • Copyright © 2021 by The American Association of Immunologists, Inc.
View Full Text

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$37.50

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

Log in using your username and password

Forgot your user name or password?
PreviousNext
Back to top

In this issue

The Journal of Immunology: 206 (3)
The Journal of Immunology
Vol. 206, Issue 3
1 Feb 2021
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about The Journal of Immunology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Dysregulation of the RIG-I–like Receptor Pathway Signaling by Peste des Petits Ruminants Virus Phosphoprotein
(Your Name) has forwarded a page to you from The Journal of Immunology
(Your Name) thought you would like to see this page from the The Journal of Immunology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Dysregulation of the RIG-I–like Receptor Pathway Signaling by Peste des Petits Ruminants Virus Phosphoprotein
Pengfei Li, Zixiang Zhu, Weijun Cao, Fan Yang, Xusheng Ma, Hong Tian, Keshan Zhang, Xiangtao Liu, Haixue Zheng
The Journal of Immunology February 1, 2021, 206 (3) 566-579; DOI: 10.4049/jimmunol.2000432

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Dysregulation of the RIG-I–like Receptor Pathway Signaling by Peste des Petits Ruminants Virus Phosphoprotein
Pengfei Li, Zixiang Zhu, Weijun Cao, Fan Yang, Xusheng Ma, Hong Tian, Keshan Zhang, Xiangtao Liu, Haixue Zheng
The Journal of Immunology February 1, 2021, 206 (3) 566-579; DOI: 10.4049/jimmunol.2000432
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Visual Abstract
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosures
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Novel Mouse Model Reveals That Serine Phosphorylation of L-Plastin Is Essential for Effective Splenic Clearance of Pneumococcus
  • Longitudinal Peripheral Blood Transcriptional Analysis Reveals Molecular Signatures of Disease Progression in COVID-19 Patients
  • African Swine Fever Virus MGF-505-7R Negatively Regulates cGAS–STING-Mediated Signaling Pathway
Show more INFECTIOUS DISEASE AND HOST RESPONSE

Similar Articles

Navigate

  • Home
  • Current Issue
  • Next in The JI
  • Archive
  • Brief Reviews
  • Pillars of Immunology
  • Translating Immunology

For Authors

  • Submit a Manuscript
  • Instructions for Authors
  • About the Journal
  • Journal Policies
  • Editors

General Information

  • Advertisers
  • Subscribers
  • Rights and Permissions
  • Accessibility Statement
  • FAR 889
  • Privacy Policy
  • Disclaimer

Journal Services

  • Email Alerts
  • RSS Feeds
  • ImmunoCasts
  • Twitter

Copyright © 2021 by The American Association of Immunologists, Inc.

Print ISSN 0022-1767        Online ISSN 1550-6606