Type I interferon underlies severe disease associated with Junín virus infection in mice

  1. Brady T Hickerson
  2. Eric J Sefing
  3. Kevin W Bailey
  4. Arnaud J Van Wettere
  5. Manuel L Penichet
  6. Brian B Gowen  Is a corresponding author
  1. Utah State University, United States
  2. University of California, Los Angeles, United States

Abstract

Junín virus (JUNV) is one of five New World mammarenaviruses (NWMs) that cause fatal hemorrhagic disease in humans and is the etiological agent of Argentine hemorrhagic fever (AHF). The pathogenesis underlying AHF is poorly understood; however, a prolonged, elevated interferon-a (IFN-a) response is associated with a negative disease outcome. A feature of all NWMs that cause viral hemorrhagic fever is the use of human transferrin receptor 1 (hTfR1) for cellular entry. Here, we show that mice expressing hTfR1 develop a lethal disease course marked by an increase in serum IFN-a concentration when challenged with JUNV. Further, we provide evidence that the type I IFN response is central to the development of severe JUNV disease in hTfR1 mice. Our findings identify TfR1-mediated entry and the type I IFN response as key factors in the pathogenesis of JUNV infection in mice.

Data availability

All data generated or analyzed during this study are included in the manuscript.

Article and author information

Author details

  1. Brady T Hickerson

    Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, United States
    Competing interests
    No competing interests declared.
  2. Eric J Sefing

    Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, United States
    Competing interests
    No competing interests declared.
  3. Kevin W Bailey

    Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, United States
    Competing interests
    No competing interests declared.
  4. Arnaud J Van Wettere

    Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, United States
    Competing interests
    No competing interests declared.
  5. Manuel L Penichet

    David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    Manuel L Penichet, is a shareholder of Klyss Biotech, Inc. The Regents of the University of California licensed Dr. Penichet's technology to this firm. The author has no other competing interests to declare..
  6. Brian B Gowen

    Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, United States
    For correspondence
    brian.gowen@usu.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9113-2575

Funding

National Institutes of Health (R56 AI13646)

  • Brian B Gowen

National Institutes of Health (R01 AI14110)

  • Brian B Gowen

National Institutes of Health (R01 CA196266)

  • Manuel L Penichet

Utah State University (Graduate Research and Creative Opportunities grant)

  • Brady T Hickerson

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

Ethics

Animal experimentation: All animal procedures complied with USDA guidelines and were conducted at the AAALAC-accredited laboratory animal research facilities at Utah State University under protocol #10034, approved by the Utah State University Institutional Animal Care and Use Committee.

Reviewing Editor

  1. John W Schoggins, University of Texas Southwestern Medical Center, United States

Publication history

  1. Received: January 21, 2020
  2. Accepted: May 25, 2020
  3. Accepted Manuscript published: May 26, 2020 (version 1)
  4. Version of Record published: June 16, 2020 (version 2)

Copyright

© 2020, Hickerson 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. Brady T Hickerson
  2. Eric J Sefing
  3. Kevin W Bailey
  4. Arnaud J Van Wettere
  5. Manuel L Penichet
  6. Brian B Gowen
(2020)
Type I interferon underlies severe disease associated with Junín virus infection in mice
eLife 9:e55352.
https://doi.org/10.7554/eLife.55352

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