Human FcRn expression and Type I Interferon signaling control Echovirus 11 pathogenesis in mice.

Autor: Wells AI; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.; Center for Microbial Pathogenesis, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America., Grimes KA; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.; Center for Microbial Pathogenesis, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America., Kim K; Kord Animal Health Diagnostic Laboratory, Nashville, Tennessee, United States of America.; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology La Jolla, California, United States of America., Branche E; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology La Jolla, California, United States of America., Bakkenist CJ; Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America., DePas WH; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.; Center for Microbial Pathogenesis, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America., Shresta S; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology La Jolla, California, United States of America., Coyne CB; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.; Center for Microbial Pathogenesis, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2021 Jan 29; Vol. 17 (1), pp. e1009252. Date of Electronic Publication: 2021 Jan 29 (Print Publication: 2021).
DOI: 10.1371/journal.ppat.1009252
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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