A picorna-like virus suppresses the N-end rule pathway to inhibit apoptosis

  1. Zhaowei Wang
  2. Xiaoling Xia
  3. Xueli Yang
  4. Xueyi Zhang
  5. Yongxiang Liu
  6. Di Wu
  7. Yuan Fang
  8. Yujie Liu
  9. Jiuyue Xu
  10. Yang Qiu
  11. Xi Zhou  Is a corresponding author
  1. Wuhan University, China
  2. Wuhan Institute of Virology, Chinese Academy of Sciences, China

Abstract

The N-end rule pathway is an evolutionarily conserved proteolytic system that degrades proteins containing N-terminal degradation signals called N-degrons, and has emerged as a key regulator of various processes. Viruses manipulate diverse host pathways to facilitate viral replication and evade antiviral defenses. However, it remains unclear if viral infection has any impact on the N-end rule pathway. Here, using a picorna-like virus as a model, we found that viral infection promoted the accumulation of caspase-cleaved Drosophila Inhibitor of Apoptosis 1 (DIAP1) by inducing the degradation of N-terminal amidohydrolase 1 (NTAN1), a key N-end rule component that identifies N-degron to initiate the process. The virus-induced NTAN1 degradation is independent of polyubiquitylation but dependent on proteasome. Furthermore, the virus-induced N-end rule pathway suppression inhibits apoptosis and benefits viral replication. Thus, our findings demonstrate that a virus can suppress the N-end rule pathway, and uncover a new mechanism for virus to evade apoptosis.

Article and author information

Author details

  1. Zhaowei Wang

    State Key Laboratory of Virology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Xiaoling Xia

    State Key Laboratory of Virology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Xueli Yang

    State Key Laboratory of Virology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Xueyi Zhang

    State Key Laboratory of Virology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Yongxiang Liu

    State Key Laboratory of Virology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Di Wu

    State Key Laboratory of Virology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Yuan Fang

    State Key Laboratory of Virology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Yujie Liu

    State Key Laboratory of Virology, Wuhan University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Jiuyue Xu

    State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Yang Qiu

    State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Xi Zhou

    State Key Laboratory of Virology, Wuhan University, Wuhan, China
    For correspondence
    zhouxi@wh.iov.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3846-5079

Funding

National Natural Science Foundation of China (No. 31522004)

  • Xi Zhou

National Natural Science Foundation of China (No. 31600126)

  • Zhaowei Wang

Academy of Medical Sciences (No. 31761130075)

  • Xi Zhou

National Basic Research Program of China (No. 2014CB542603)

  • Xi Zhou

National High-Tech R&D Program of China (No. 2015AA020939)

  • Xi Zhou

Strategic Priority Research Program of Chinese Academy of Sciences (No. XDPB0301)

  • Xi Zhou

Natural Science Foundation of Hubei Province (No. 2016CFA045)

  • Xi Zhou

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2017, Wang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,359
    views
  • 511
    downloads
  • 19
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Citations by DOI

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Zhaowei Wang
  2. Xiaoling Xia
  3. Xueli Yang
  4. Xueyi Zhang
  5. Yongxiang Liu
  6. Di Wu
  7. Yuan Fang
  8. Yujie Liu
  9. Jiuyue Xu
  10. Yang Qiu
  11. Xi Zhou
(2017)
A picorna-like virus suppresses the N-end rule pathway to inhibit apoptosis
eLife 6:e30590.
https://doi.org/10.7554/eLife.30590

Share this article

https://doi.org/10.7554/eLife.30590