Self-capping of nucleoprotein filaments protects Newcastle Disease Virus genome

  1. Xiyong Song
  2. Hong Shan
  3. Yanping Zhu
  4. Shunlin Hu
  5. Ling Xue
  6. Yong Chen
  7. Wei Ding
  8. Tongxin Niu
  9. Jian Gu
  10. Songying Ouyang  Is a corresponding author
  11. Qing-Tao Shen  Is a corresponding author
  12. Zhi-Jie Liu  Is a corresponding author
  1. Kunming Medical University, China
  2. ShanghaiTech University, China
  3. Chinese Academy of Sciences, China
  4. Yangzhou University, China
  5. Fujian Normal University, China

Abstract

Non-segmented negative-strand RNA viruses, such as Measles, Ebola and Newcastle disease viruses (NDV), encapsidate viral genomic RNAs into helical nucleocapsids which serve as the template for viral replication and transcription. Here, the clam-shaped nucleocapsid structure, where the NDV viral genome is sequestered, was determined at 4.8 Å resolution by cryo-electron microscopy. The clam-shaped structure is composed of two single-turn spirals packed in a back-to-back mode, and the tightly packed structure functions as a seed for nucleocapsid to assemble from both directions and grows into double-headed filaments with two separate RNA strings inside. Disruption of this structure by mutations on its loop interface yielded a single-headed unfunctional filament.

Data availability

The cryo-EM density map has been deposited in EMDB with the accession number EMD-9793. The atom coordinates of the structure have been deposited in PDB with the PDB ID 6JC3.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Xiyong Song

    Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Hong Shan

    iHuman Institute, ShanghaiTech University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Yanping Zhu

    National Laboratory of Biomacromolecules, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Shunlin Hu

    College of Veterinary Medicine, Yangzhou University, Yangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Ling Xue

    College of Veterinary Medicine, Yangzhou University, Yangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Yong Chen

    National Laboratory of Biomacromolecules, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Wei Ding

    Center for Biological Imaging, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Tongxin Niu

    Center for Biological Imaging, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Jian Gu

    College of Veterinary Medicine, Yangzhou University, Yangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Songying Ouyang

    College of Life Sciences, Fujian Normal University, Fuzhou, China
    For correspondence
    ouyangsy@fjnu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  11. Qing-Tao Shen

    iHuman Institute, ShanghaiTech University, Shanghai, China
    For correspondence
    shenqt@shanghaitech.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  12. Zhi-Jie Liu

    Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, China
    For correspondence
    liuzhj@shanghaiTech.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7279-2893

Funding

National Nature Science Foundation of China grant (31330019)

  • Zhi-Jie Liu

National Nature Science Foundation of China grant (31770948)

  • Songying Ouyang

National Nature Science Foundation of China grant (31570875)

  • Songying Ouyang

National Natural Science Foundation of China grant (81590761)

  • Songying Ouyang

the National Key R&D program of China (2017YFA0504800)

  • Qing-Tao Shen

Yunnan Provincial Science and Technology Department Project (2016FC007)

  • Zhi-Jie Liu

The Pujiang Talent program (17PJ1406700)

  • Qing-Tao Shen

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

Reviewing Editor

  1. David M Knipe, Harvard Medical School, United States

Version history

  1. Received: January 10, 2019
  2. Accepted: July 9, 2019
  3. Accepted Manuscript published: July 10, 2019 (version 1)
  4. Version of Record published: August 1, 2019 (version 2)

Copyright

© 2019, Song 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

  • 1,955
    views
  • 302
    downloads
  • 19
    citations

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

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. Xiyong Song
  2. Hong Shan
  3. Yanping Zhu
  4. Shunlin Hu
  5. Ling Xue
  6. Yong Chen
  7. Wei Ding
  8. Tongxin Niu
  9. Jian Gu
  10. Songying Ouyang
  11. Qing-Tao Shen
  12. Zhi-Jie Liu
(2019)
Self-capping of nucleoprotein filaments protects Newcastle Disease Virus genome
eLife 8:e45057.
https://doi.org/10.7554/eLife.45057

Share this article

https://doi.org/10.7554/eLife.45057

Further reading

    1. Microbiology and Infectious Disease
    Brian G Vassallo, Noemie Scheidel ... Dennis H Kim
    Research Article

    The microbiota is a key determinant of the physiology and immunity of animal hosts. The factors governing the transmissibility of viruses between susceptible hosts are incompletely understood. Bacteria serve as food for Caenorhabditis elegans and represent an integral part of the natural environment of C. elegans. We determined the effects of bacteria isolated with C. elegans from its natural environment on the transmission of Orsay virus in C. elegans using quantitative virus transmission and host susceptibility assays. We observed that Ochrobactrum species promoted Orsay virus transmission, whereas Pseudomonas lurida MYb11 attenuated virus transmission relative to the standard laboratory bacterial food Escherichia coli OP50. We found that pathogenic Pseudomonas aeruginosa strains PA01 and PA14 further attenuated virus transmission. We determined that the amount of Orsay virus required to infect 50% of a C. elegans population on P. lurida MYb11 compared with Ochrobactrum vermis MYb71 was dramatically increased, over three orders of magnitude. Host susceptibility was attenuated even further in the presence of P. aeruginosa PA14. Genetic analysis of the determinants of P. aeruginosa required for attenuation of C. elegans susceptibility to Orsay virus infection revealed a role for regulators of quorum sensing. Our data suggest that distinct constituents of the C. elegans microbiota and potential pathogens can have widely divergent effects on Orsay virus transmission, such that associated bacteria can effectively determine host susceptibility versus resistance to viral infection. Our study provides quantitative evidence for a critical role for tripartite host-virus-bacteria interactions in determining the transmissibility of viruses among susceptible hosts.

    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease
    Carlo Giannangelo, Matthew P Challis ... Darren J Creek
    Research Article

    New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria drug resistance. Here, we describe the multi-omic chemical validation of Plasmodium M1 alanyl metalloaminopeptidase as an attractive drug target using the selective inhibitor, MIPS2673. MIPS2673 demonstrated potent inhibition of recombinant Plasmodium falciparum (PfA-M1) and Plasmodium vivax (PvA-M1) M1 metalloaminopeptidases, with selectivity over other Plasmodium and human aminopeptidases, and displayed excellent in vitro antimalarial activity with no significant host cytotoxicity. Orthogonal label-free chemoproteomic methods based on thermal stability and limited proteolysis of whole parasite lysates revealed that MIPS2673 solely targets PfA-M1 in parasites, with limited proteolysis also enabling estimation of the binding site on PfA-M1 to within ~5 Å of that determined by X-ray crystallography. Finally, functional investigation by untargeted metabolomics demonstrated that MIPS2673 inhibits the key role of PfA-M1 in haemoglobin digestion. Combined, our unbiased multi-omic target deconvolution methods confirmed the on-target activity of MIPS2673, and validated selective inhibition of M1 alanyl metalloaminopeptidase as a promising antimalarial strategy.