Type I interferon underlies severe disease associated with Junin virus infection in mice
Open Access
- 26 May 2020
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
Abstract
Junin virus (JUNV) is one of five New World mammarenaviruses (NWMs) that causes 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-alpha (IFN-alpha) 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-alpha 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 hTfR1-mediated entry and the type I IFN response as key factors in the pathogenesis of JUNV infection in mice.Funding Information
- National Institutes of Health (R56 AI13646)
- National Institutes of Health (R01 AI14110)
- National Institutes of Health (R01 CA196266)
- Utah State University (Graduate Research and Creative Opportunities grant)
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