1. Microbiology and Infectious Disease
Download icon

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
Research Article
  • Cited 0
  • Views 641
  • Annotations
Cite this article as: eLife 2020;9:e50999 doi: 10.7554/eLife.50999

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.

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.

Reviewing Editor

  1. Sara L Sawyer, University of Colorado Boulder, United States

Publication history

  1. Received: August 9, 2019
  2. Accepted: October 8, 2020
  3. Accepted Manuscript published: October 21, 2020 (version 1)
  4. Version of Record published: November 9, 2020 (version 2)

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.

Metrics

  • 641
    Page views
  • 122
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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)

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

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

Further reading

    1. Ecology
    2. Microbiology and Infectious Disease
    Lara Urban et al.
    Research Article

    While traditional microbiological freshwater tests focus on the detection of specific bacterial indicator species, including pathogens, direct tracing of all aquatic DNA through metagenomics poses a profound alternative. Yet, in situ metagenomic water surveys face substantial challenges in cost and logistics. Here, we present a simple, fast, cost-effective and remotely accessible freshwater diagnostics workflow centred around the portable nanopore sequencing technology. Using defined compositions and spatiotemporal microbiota from surface water of an example river in Cambridge (UK), we provide optimised experimental and bioinformatics guidelines, including a benchmark with twelve taxonomic classification tools for nanopore sequences. We find that nanopore metagenomics can depict the hydrological core microbiome and fine temporal gradients in line with complementary physicochemical measurements. In a public health context, these data feature relevant sewage signals and pathogen maps at species level resolution. We anticipate that this framework will gather momentum for new environmental monitoring initiatives using portable devices.

    1. Microbiology and Infectious Disease
    Philip P Adams et al.
    Research Article

    Many bacterial genes are regulated by RNA elements in their 5´ untranslated regions (UTRs). However, the full complement of these elements is not known even in the model bacterium Escherichia coli. Using complementary RNA-sequencing approaches, we detected large numbers of 3´ ends in 5´ UTRs and open reading frames (ORFs), suggesting extensive regulation by premature transcription termination. We documented regulation for multiple transcripts, including spermidine induction involving Rho and translation of an upstream ORF for an mRNA encoding a spermidine efflux pump. In addition to discovering novel sites of regulation, we detected short, stable RNA fragments derived from 5´ UTRs and sequences internal to ORFs. Characterization of three of these transcripts, including an RNA internal to an essential cell division gene, revealed that they have independent functions as sRNA sponges. Thus, these data uncover an abundance of cis- and trans-acting RNA regulators in bacterial 5´ UTRs and internal to ORFs.