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- Title
Human FcRn expression and Type I Interferon signaling control Echovirus 11 pathogenesis in mice.
- Authors
Wells, Alexandra I.; Grimes, Kalena A.; Kim, Kenneth; Branche, Emilie; Bakkenist, Christopher J.; DePas, William H.; Shresta, Sujan; Coyne, Carolyn B.
- Abstract
Neonatal echovirus infections are characterized by severe hepatitis and neurological complications that can be fatal. Here, we show that expression of the human homologue of the neonatal Fc receptor (hFcRn), the primary receptor for echoviruses, and ablation of type I interferon (IFN) signaling are key host determinants involved in echovirus pathogenesis. We show that expression of hFcRn alone is insufficient to confer susceptibility to echovirus infections in mice. However, expression of hFcRn in mice deficient in type I interferon (IFN) signaling, hFcRn-IFNAR-/-, recapitulate the echovirus pathogenesis observed in humans. Luminex-based multianalyte profiling from E11 infected hFcRn-IFNAR-/- mice revealed a robust systemic immune response to infection, including the induction of type I IFNs. Furthermore, similar to the severe hepatitis observed in humans, E11 infection in hFcRn-IFNAR-/- mice caused profound liver damage. Our findings define the host factors involved in echovirus pathogenesis and establish in vivo models that recapitulate echovirus disease in humans. Author summary: Echoviruses severely impact the health children and neonates worldwide. Although echoviruses cause such severe disease complications, no animals models have been established to understand how the virus causes these complications. Here, we establish a suckling pup and adult mouse model of echovirus pathogenesis. We use mice that express the human form of the viral entry receptor, FcRn, since wild type mice do not support infection. We found that in these mice, the main tissue site of infection is the liver, similar to human disease. We were able to show that hepatocytes in the liver are the main target of echovirus infection in mice. Additionally, these mice mount an immune response which can be used to study how the immune system responds to echovirus infection and to test novel therapeutics against echoviruses.
- Subjects
TYPE I interferons; MICE; FC receptors; INTERFERON receptors; NEONATAL infections; DISEASE complications; ECHO viruses
- Publication
PLoS Pathogens, 2021, Vol 17, Issue 1, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1009252