Skip to main content

Main menu

  • 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
  • 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

KAP1-Mediated Epigenetic Suppression in Anti-RNA Viral Responses by Direct Targeting RIG-I and MDA5

Qi Li, Ying Qin, Wenwen Wang, Mutian Jia, Wei Zhao and Chunyuan Zhao
J Immunol October 1, 2021, 207 (7) 1903-1910; DOI: https://doi.org/10.4049/jimmunol.2100342
Qi Li
*Department of Pathogenic Biology and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Qi Li
Ying Qin
*Department of Pathogenic Biology and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wenwen Wang
*Department of Pathogenic Biology and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Wenwen Wang
Mutian Jia
*Department of Pathogenic Biology and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mutian Jia
Wei Zhao
*Department of Pathogenic Biology and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Wei Zhao
Chunyuan Zhao
†Department of Cell Biology, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Chunyuan Zhao
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF
Loading

Key Points

  • KAP1 inhibits RLR pathway.

  • KAP1 deficiency enhances anti-RNA viral innate responses.

  • KAP1 promotes repressive histone marks establishment at promoters of Ddx58 and Ifih1.

Abstract

Retinoic acid–inducible gene-I (RIG-I)–like receptors (RLRs), including RIG-I (encoded by Ddx58) and melanoma differentiation–associated gene 5 (MDA5) (encoded by Ifih1), are crucial for initiating antiviral responses. Endogenous retroviral elements (ERVs) are transposable elements derived from exogenous retroviruses that are integrated into the genome. KRAB-associated protein 1 (KAP1) is a key epigenetic suppressor of ERVs that protects cells from detrimental genome instability. Increased ERV transcripts are sensed by RLRs and trigger innate immune signaling. However, whether KAP1 directly controls RLRs activity remains unclear. In this study, we show that KAP1 attenuates RNA viral infection–induced type I IFNs and facilitates viral replication by inhibiting RIG-I/MDA5 expression in primary peritoneal macrophages (PMs) of C57BL/6J mice. Kap1 deficiency increases IFN-β expression and inhibits vesicular stomatitis virus replication in C57BL/6J mice in vivo. Mechanistically, KAP1 binds to the promoter regions of Ddx58 and Ifih1 and promotes the establishment of repressive histone marks in primary PMs of C57BL/6J mice. Concordantly, KAP1 suppresses the expression of RIG-I and MDA5 at the transcriptional level in primary PMs of C57BL/6J mice. Our results establish that KAP1 epigenetically suppresses host antiviral responses by directly targeting RIG-1 and MDA5, thus facilitating the immune escape of RNA viruses.

This article is featured in Top Reads, p.

Footnotes

  • This work was supported by grants from National Natural Science Foundation of China (81622030, 31870866, 81901609, and 81861130369) and the Academy of Medical Sciences.

  • The online version of this article contains supplemental material.

  • Abbreviations used in this article

    ERV
    endogenous retroviral element
    ChIP
    chromatin IP
    ChIP-seq
    ChIP coupled with high-throughput sequencing
    HA
    hemagglutinin
    HEK
    human embryonic kidney
    HMW
    high m.w.
    IP
    immunoprecipitation
    IRF3
    IFN regulatory factor 3
    KAP1
    Kruppel-associated box–associated protein 1
    LMW
    low m.w.
    MAVS
    mitochondrial antiviral signaling
    PM
    peritoneal macrophage
    qPCR
    quantitative PCR
    RIG-I
    retinoic acid–inducible gene-I
    RLR
    RIG-I–like receptor
    SeV
    Sendai virus
    siRNA
    small interfering RNA
    TRIM28
    tripartite motif-containing protein 28
    VSV
    vesicular stomatitis virus
    WT
    wild type

  • Received April 12, 2021.
  • Accepted July 26, 2021.
  • 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: 207 (7)
The Journal of Immunology
Vol. 207, Issue 7
1 Oct 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.
KAP1-Mediated Epigenetic Suppression in Anti-RNA Viral Responses by Direct Targeting RIG-I and MDA5
(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
KAP1-Mediated Epigenetic Suppression in Anti-RNA Viral Responses by Direct Targeting RIG-I and MDA5
Qi Li, Ying Qin, Wenwen Wang, Mutian Jia, Wei Zhao, Chunyuan Zhao
The Journal of Immunology October 1, 2021, 207 (7) 1903-1910; DOI: 10.4049/jimmunol.2100342

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
KAP1-Mediated Epigenetic Suppression in Anti-RNA Viral Responses by Direct Targeting RIG-I and MDA5
Qi Li, Ying Qin, Wenwen Wang, Mutian Jia, Wei Zhao, Chunyuan Zhao
The Journal of Immunology October 1, 2021, 207 (7) 1903-1910; DOI: 10.4049/jimmunol.2100342
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • 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

  • A Novel Ig Domain–Containing C-Type Lectin Triggers the Intestine–Hemocyte Axis to Regulate Antibacterial Immunity in Crab
  • Carbon Dioxide Sensing by Immune Cells Occurs through Carbonic Anhydrase 2–Dependent Changes in Intracellular pH
  • Neutrophil Protein Kinase R Mediates Endothelial Adhesion and Migration by the Promotion of Neutrophil Actin Polymerization
Show more INNATE IMMUNITY AND INFLAMMATION

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 © 2022 by The American Association of Immunologists, Inc.

Print ISSN 0022-1767        Online ISSN 1550-6606