A single mutation in Crimean-Congo hemorrhagic fever virus discovered in ticks impairs infectivity in human cells

  1. Brian L Hua
  2. Florine EM Scholte
  3. Valerie Ohlendorf
  4. Anne Kopp
  5. Marco Marklewitz
  6. Christian Drosten
  7. Stuart T Nichol
  8. Christina Spiropoulou
  9. Sandra Junglen  Is a corresponding author
  10. Éric Bergeron  Is a corresponding author
  1. Centers for Disease Control and Prevention, United States
  2. Charité-Universitätsmedizin Berlin, Germany
  3. Charité - Universitätsmedizin Berlin, Germany
  4. Charité Universitätsmedizin, Germany

Abstract

Crimean-Congo Hemorrhagic Fever (CCHF) is the most widely distributed tick-borne viral infection in the world. Strikingly, reported mortality rates for CCHF are extremely variable, ranging from 5 to 80% (1). CCHF virus (CCHFV, Nairoviridae) exhibits extensive genomic sequence diversity across strains (2, 3). It is currently unknown if genomic diversity is a factor contributing to variation in its pathogenicity. We obtained complete genome sequences of CCHFV directly from the tick reservoir. These new strains belong to a solitary lineage named Europe 2 that is circumstantially reputed to be less pathogenic than the epidemic strains from Europe 1 lineage. We identified a single tick-specific amino acid variant in the viral glycoprotein region that dramatically reduces its fusion activity in human cells, providing evidence that a GPC variant, present in ticks, have severely impaired function in human cells.

Data availability

All sequencing data have been deposited in GB under accession codes MK299338, MK299339, MK299340, MK299341, MK299342, MK299343, MK299344, MK299345 and MK299346

Article and author information

Author details

  1. Brian L Hua

    Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7580-3399
  2. Florine EM Scholte

    Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Valerie Ohlendorf

    Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Anne Kopp

    Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Marco Marklewitz

    Institute of Virology, Charité - Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1828-8770
  6. Christian Drosten

    Institute of Virology, Charité Universitätsmedizin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Stuart T Nichol

    Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Christina Spiropoulou

    Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8406-3161
  9. Sandra Junglen

    Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany
    For correspondence
    sandra.junglen@charite.de
    Competing interests
    The authors declare that no competing interests exist.
  10. Éric Bergeron

    Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, United States
    For correspondence
    ebergeron@cdc.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3398-8628

Funding

American Society for Microbiology

  • Brian L Hua

Centers for Disease Control and Prevention

  • Stuart T Nichol
  • Christina Spiropoulou
  • Éric Bergeron

Federal Ministry of Education and Research (01KI1716)

  • Sandra Junglen

German Center for Infection Research (TTU 01.801)

  • Christian Drosten

National Institutes of Health (R01AI109008)

  • Éric Bergeron

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

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Brian L Hua
  2. Florine EM Scholte
  3. Valerie Ohlendorf
  4. Anne Kopp
  5. Marco Marklewitz
  6. Christian Drosten
  7. Stuart T Nichol
  8. Christina Spiropoulou
  9. Sandra Junglen
  10. Éric Bergeron
(2020)
A single mutation in Crimean-Congo hemorrhagic fever virus discovered in ticks impairs infectivity in human cells
eLife 9:e50999.
https://doi.org/10.7554/eLife.50999

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https://doi.org/10.7554/eLife.50999