A Serpin Shapes the Extracellular Environment to Prevent Influenza A Virus Maturation

作者：Dittmann Meike; Hoffmann Hans Heinrich; Scull Margaret A; Gilmore Rachel H; Bell Kierstin L; Ciancanelli Michael; Wilson Sam J; Crotta Stefania; Yu Yingpu; Flatley Brenna; Xiao Jing W; Casanova Jean Laurent; Wack Andreas; Bieniasz Paul D; Rice Charles M^*

来源：Cell, 2015, 160(4): 631-643.

DOI：10.1016/j.cell.2015.01.040

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.

• 出版日期2015-2-12
• 单位河北医科大学