Abstract

Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne febrile illness with wide geographic distribution. CCHF is caused by infection with the Crimean-Congo hemorrhagic fever virus (CCHFV) and case fatality rates can be as high as 30%. Despite causing severe disease in humans, our understanding of the host and viral determinants of CCHFV pathogenesis are limited. A major limitation in the investigation of CCHF has been the lack of suitable small animal models. Wild-type mice are resistant to clinical isolates of CCHFV and consequently, mice must be deficient in type I interferon responses to study the more severe aspects of CCHFV. We report here a mouse-adapted variant of CCHFV that recapitulates in adult, immunocompetent mice the severe CCHF observed in humans. This mouse-adapted variant of CCHFV significantly improves our ability to study host and viral determinants of CCHFV-induced disease in a highly tractable mouse model.

Data availability

Relevant source data for figures is provided and the consensus sequence of MA-CCHFV has been deposited to Genbank (Accession #s MW058028 - MW058030)

Article and author information

Author details

  1. David W Hawman

    Laboratory of Virology, NIAID/NIH, Hamilton, United States
    For correspondence
    david.hawman@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8233-8176
  2. Kimberly Meade-White

    Laboratory of Virology, NIAID/NIH, Hamilton, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Shanna Leventhal

    Laboratory of Virology, NIAID/NIH, Hamilton, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Friederike Feldmann

    Laboratory of Virology, NIAID/NIH, Hamilton, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Atsushi Okumura

    Laboratory of Virology, NIAID/NIH, Hamilton, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Brian Smith

    Texas Veterinary Pathology, Texas Veterinary Pathology, Spring Branch, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Dana Scott

    Rocky Mountain Veterinary Branch, NIAID/NIH, Hamilton, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Heinz Feldmann

    Rocky Mountain Veterinary Branch, NIAID/NIH, Hamilton, United States
    For correspondence
    feldmannh@niaid.nih.gov
    Competing interests
    The authors declare that no competing interests exist.

Funding

Department of Intramural Research, NIH

  • David W Hawman

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

Reviewing Editor

  1. Amy Hartman, University of Pittsburgh

Ethics

Animal experimentation: Animal experiments were approved by the institutional animal care and use committee, protocol #s 2017-68 and 2019-63. Studies performed by experienced personnel under veterinary oversight. Mice were group-housed in HEPA-filtered cage systems and acclimatized to BSL4 conditions prior to start of the experiment. They were provided with nesting material and food and water ad libitum.

Version history

  1. Received: October 10, 2020
  2. Accepted: January 7, 2021
  3. Accepted Manuscript published: January 8, 2021 (version 1)
  4. Version of Record published: January 15, 2021 (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.

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  1. David W Hawman
  2. Kimberly Meade-White
  3. Shanna Leventhal
  4. Friederike Feldmann
  5. Atsushi Okumura
  6. Brian Smith
  7. Dana Scott
  8. Heinz Feldmann
(2021)
Immunocompetent mouse model for Crimean-Congo hemorrhagic fever virus
eLife 10:e63906.
https://doi.org/10.7554/eLife.63906

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https://doi.org/10.7554/eLife.63906

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