The immune response can intervene at various points in the life cycle of a virus. In Cell, Rice and colleagues screen interferon-stimulated genes to identify cell-intrinsic factors involved in resistance to influenza A virus (IAV). One such factor, the plasminogen-activator inhibitor PAI-1, substantially diminishes infection with IAV. Both IAV and interferon-β trigger production of PAI-1 and its release into the extracellular medium. As a final maturation step during budding, certain viruses such as IAV require cleavage of glycoproteins by host proteases. PAI-1 inhibits proteases relevant to this cleavage, such as tryptase, which results in non-infectious IAV particles. Mice deficient in PAI-1 show slightly diminished survival and worse pathology after infection with IAV. Fibroblasts derived from patients with deficiencies in the production of extracellular PAI-1 show impaired control of infection with IAV. This study therefore identifies a mechanism that controls the spread of IAV by targeting the terminal stage of the viral life cycle.

Cell (12 February 2015) doi:10.1016/j.cell.2015.01.040