An innate defense peptide BPIFA1/SPLUNC1 restricts influenza A virus infection.

Autor: Akram KM; Academic Unit of Respiratory Medicine, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK., Moyo NA; Department of Infection Biology, University of Liverpool, Liverpool, UK., Leeming GH; Department of Infection Biology, University of Liverpool, Liverpool, UK.; Department of Veterinary Pathology, University of Liverpool, Liverpool, UK., Bingle L; Academic Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, UK., Jasim S; The Roslin Institute, University of Edinburgh, Edinburgh, UK., Hussain S; The Roslin Institute, University of Edinburgh, Edinburgh, UK., Schorlemmer A; Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA., Kipar A; Department of Infection Biology, University of Liverpool, Liverpool, UK.; Department of Veterinary Pathology, University of Liverpool, Liverpool, UK.; Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland., Digard P; The Roslin Institute, University of Edinburgh, Edinburgh, UK., Tripp RA; Department of Infectious Diseases, University of Georgia, Athens, Georgia, USA., Shohet RV; Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA., Bingle CD; Academic Unit of Respiratory Medicine, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK., Stewart JP; Department of Infection Biology, University of Liverpool, Liverpool, UK.
Jazyk: angličtina
Zdroj: Mucosal immunology [Mucosal Immunol] 2018 Jan; Vol. 11 (1), pp. 71-81. Date of Electronic Publication: 2017 May 17.
DOI: 10.1038/mi.2017.45
Abstrakt: The airway epithelium secretes proteins that function in innate defense against infection. Bactericidal/permeability-increasing fold-containing family member A1 (BPIFA1) is secreted into airways and has a protective role during bacterial infections, but it is not known whether it also has an antiviral role. To determine a role in host defense against influenza A virus (IAV) infection and to find the underlying defense mechanism, we developed transgenic mouse models that are deficient in BPIFA1 and used these, in combination with in vitro three-dimensional mouse tracheal epithelial cell (mTEC) cultures, to investigate its antiviral properties. We show that BPIFA1 has a significant role in mucosal defense against IAV infection. BPIFA1 secretion was highly modulated after IAV infection. Mice deficient in BPIFA1 lost more weight after infection, supported a higher viral load and virus reached the peripheral lung earlier, indicative of a defect in the control of infection. Further analysis using mTEC cultures showed that BPIFA1-deficient cells bound more virus particles, displayed increased nuclear import of IAV ribonucleoprotein complexes, and supported higher levels of viral replication. Our results identify a critical role of BPIFA1 in the initial phase of infection by inhibiting the binding and entry of IAV into airway epithelial cells.
Databáze: MEDLINE
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