Type I interferon underlies severe disease associated with Junín virus infection in mice
- Utah State University, United States
- 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.
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Author details
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.
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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Type I interferon underlies severe disease associated with Junín virus infection in mice
eLife 9:e55352.
https://doi.org/10.7554/eLife.55352
