1. Evolutionary Biology
  2. Microbiology and Infectious Disease
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Globally defining the effects of mutations in a picornavirus capsid

  1. Florian Mattenberger
  2. Victor Latorre
  3. Omer Tirosh
  4. Adi Stern
  5. Ron Geller  Is a corresponding author
  1. Universitat de Valencia, Spain
  2. Tel Aviv University, Israel
Research Article
  • Cited 2
  • Views 905
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Cite this article as: eLife 2021;10:e64256 doi: 10.7554/eLife.64256

Abstract

The capsids of non-enveloped viruses are highly multimeric and multifunctional protein assemblies that play key roles in viral biology and pathogenesis. Despite their importance, a comprehensive understanding of how mutations affect viral fitness across different structural and functional attributes of the capsid is lacking. To address this limitation, we globally define the effects of mutations across the capsid of a human picornavirus. Using this resource, we identify structural and sequence determinants that accurately predict mutational fitness effects, refine evolutionary analyses, and define the sequence specificity of key capsid encoded motifs. Furthermore, capitalizing on the derived sequence requirements for capsid encoded protease cleavage sites, we implement a bioinformatic approach for identifying novel host proteins targeted by viral proteases. Our findings represent the most comprehensive investigation of mutational fitness effects in a picornavirus capsid to date and illuminate important aspects of viral biology, evolution, and host interactions.

Data availability

Sequencing data have been uploaded to SRA (Bioproject PRJNA643896, SRA SRP269871, Accession SRX8663374-SRX8663384). All data used in the paper are either included as supplemental data and/or can be found at https://github.com/RGellerLab/CVB3_Capsid_DMS.

The following data sets were generated

Article and author information

Author details

  1. Florian Mattenberger

    Institute for Integrative Systems Biology, Universitat de Valencia, Paterna, Spain
    Competing interests
    The authors declare that no competing interests exist.
  2. Victor Latorre

    Institute for Integrative Systems Biology, Universitat de Valencia, Paterna, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Omer Tirosh

    School of Molecular Cell Biology and Biotechnology, Tel Aviv University, Tel-Aviv, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Adi Stern

    School of Molecular Cell Biology and Biotechnology, Tel Aviv University, Tel-Aviv, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2919-3542
  5. Ron Geller

    Institute for Integrative Systems Biology, Universitat de Valencia, Paterna, Spain
    For correspondence
    ron.geller@uv.es
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7612-4611

Funding

Ministerio de Ciencia, Innovación y Universidades (BFU2017-86094-R)

  • Ron Geller

Ministerio de Economía, Industria y Competitividad, Gobierno de España (RYC-2015-17517)

  • Ron Geller

Ministerio de Economía, Industria y Competitividad, Gobierno de España (BES-2016-076677)

  • Florian Mattenberger

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

Reviewing Editor

  1. Jan E Carette, Stanford University School of Medicine, United States

Publication history

  1. Received: October 22, 2020
  2. Accepted: January 11, 2021
  3. Accepted Manuscript published: January 12, 2021 (version 1)
  4. Version of Record published: February 4, 2021 (version 2)

Copyright

© 2021, Mattenberger 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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