CpG and UpA dinucleotides in both coding and non-coding regions of echovirus 7 inhibit replication initiation post-entry

  1. Jelke Jan Fros  Is a corresponding author
  2. Isabelle Dietrich
  3. Kinda Alshaikhahmed
  4. Tim Casper Passchier
  5. David John Evans
  6. Peter Simmonds  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. University of St. Andrews, United Kingdom

Abstract

Most vertebrate and plant RNA and small DNA viruses suppress genomic CpG and UpA dinucleotide frequencies, apparently mimicking host mRNA composition. Artificially increasing CpG/UpA dinucleotides attenuates viruses through an entirely unknown mechanism. Using the echovirus 7 (E7) model in several cell types, we show that the restriction in E7 replication in mutants with increased CpG/UpA dinucleotides occurred immediately after viral entry, with incoming virions failing to form replication complexes. Sequences of CpG/UpA-high virus stocks showed no evidence of increased mutational errors that would render them replication defective, these viral RNAs were not differentially sequestered in cytoplasmic stress granules nor did they induce a systemic antiviral state. Importantly, restriction was not mediated through effects on translation efficiency since replicons with high CpG/UpA sequences inserted into a non-coding region were similarly replication defective. Host-cells thus possess intrinsic defence pathways that prevent replication of viruses with increased CpG/UpA frequencies independently of codon usage.

Article and author information

Author details

  1. Jelke Jan Fros

    Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom
    For correspondence
    jelke.fros@ndm.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3291-8401
  2. Isabelle Dietrich

    Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Kinda Alshaikhahmed

    Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Tim Casper Passchier

    Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. David John Evans

    Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Peter Simmonds

    Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom
    For correspondence
    peter.simmonds@ndm.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Funding

Wellcome (WT103767MA)

  • Peter Simmonds

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

Reviewing Editor

  1. Steve Goodbourn, Institute for Infection and Immunity, St. George's, University of London

Version history

  1. Received: June 1, 2017
  2. Accepted: September 28, 2017
  3. Accepted Manuscript published: September 29, 2017 (version 1)
  4. Version of Record published: October 27, 2017 (version 2)
  5. Version of Record updated: November 2, 2017 (version 3)

Copyright

© 2017, Fros 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.

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  1. Jelke Jan Fros
  2. Isabelle Dietrich
  3. Kinda Alshaikhahmed
  4. Tim Casper Passchier
  5. David John Evans
  6. Peter Simmonds
(2017)
CpG and UpA dinucleotides in both coding and non-coding regions of echovirus 7 inhibit replication initiation post-entry
eLife 6:e29112.
https://doi.org/10.7554/eLife.29112

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https://doi.org/10.7554/eLife.29112

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