A Serpin shapes the extracellular environment to prevent influenza A virus maturation

Dittmann, M. et al. (2015) A Serpin shapes the extracellular environment to prevent influenza A virus maturation. Cell, 160(4), pp. 631-643. (doi: 10.1016/j.cell.2015.01.040) (PMID:25679759) (PMCID:PMC4328142)

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Abstract

Interferon-stimulated genes (ISGs) act in concert to provide a tight barrier against viruses. Recent studies have shed light on the contribution of individual ISG effectors to the antiviral state, but most have examined those acting on early, intracellular stages of the viral life cycle. Here, we applied an image-based screen to identify ISGs inhibiting late stages of influenza A virus (IAV) infection. We unraveled a directly antiviral function for the gene SERPINE1, encoding plasminogen activator inhibitor 1 (PAI-1). By targeting extracellular airway proteases, PAI-1 inhibits IAV glycoprotein cleavage, thereby reducing infectivity of progeny viruses. This was biologically relevant for IAV restriction in vivo. Further, partial PAI-1 deficiency, attributable to a polymorphism in human SERPINE1, conferred increased susceptibility to IAV in vitro. Together, our findings reveal that manipulating the extracellular environment to inhibit the last step in a virus life cycle is an important mechanism of the antiviral response.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Flatley, Miss Brenna and Wilson, Professor Sam
Authors: Dittmann, M., Hoffmann, H.-H., Scull, M. A., Gilmore, R. H., Bell, K. L., Ciancanelli, M., Wilson, S. J., Crotta, S., Yu, Y., Flatley, B., Xiao, J. W., Casanova, J.-L., Wack, A., Bieniasz, P. D., and Rice, C. M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Cell
Publisher:Elsevier (Cell Press)
ISSN:0092-8674
ISSN (Online):1097-4172
Copyright Holders:Copyright © 2015 Elsevier Inc.
First Published:First published in Cell 160(4):631-643
Publisher Policy:Reproduced under a Creative Commons License

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