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The Serine Proteinase Inhibitor (Serpin) Plasminogen Activation Inhibitor Type 2 Protects against Viral Cytopathic Effects by Constitutive Interferon α/β Priming

By Toni M. Antalis, May La Linn, Karen Donnan, Luis Mateo, Joy Gardner, Joanne L. Dickinson, Kathy Buttigieg and Andreas Suhrbier


The serine proteinase inhibitor (serpin) plasminogen activator inhibitor type 2 (PAI-2) is well characterized as an inhibitor of extracellular urokinase-type plasminogen activator. Here we show that intracellular, but not extracellular, PAI-2 protected cells from the rapid cytopathic effects of alphavirus infection. This protection did not appear to be related to an effect on apoptosis but was associated with a PAI-2–mediated induction of constitutive low-level interferon (IFN)-α/β production and IFN-stimulated gene factor 3 (ISGF3) activation, which primed the cells for rapid induction of antiviral genes. This primed phenotype was associated with a rapid development of resistance to infection by the PAI-2 transfected cells and the establishment of a persistent productive infection. PAI-2 was also induced in macrophages in response to viral RNA suggesting that PAI-2 is a virus response gene. These observations, together with the recently demonstrated PAI-2–mediated inhibition of tumor necrosis factor-α induced apoptosis, (a) illustrate that PAI-2 has an additional and distinct function as an intracellular regulator of signal transduction pathway(s) and (b) demonstrate a novel activity for a eukaryotic serpin

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Publisher: The Rockefeller University Press
OAI identifier: oai:pubmedcentral.nih.gov:2212304
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