eCite Digital Repository

The serine proteinase inhibitor (Serpin) plasminogen activation inhibitor type 2 protects against viral cytopathic effects by constitutive interferon alpha/beta priming

Citation

Antalis, TM and Linn, ML and Donnan, K and Mateo, L and Gardner, J and Dickinson, JL and Buttigieg, K and Suhrbier, A, The serine proteinase inhibitor (Serpin) plasminogen activation inhibitor type 2 protects against viral cytopathic effects by constitutive interferon alpha/beta priming, Journal of Experimental Medicine, 187, (11) pp. 1799-1811. ISSN 0022-1007 (1998) [Refereed Article]

DOI: doi:10.1084/jem.187.11.1799

Abstract

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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Medical Biochemistry and Metabolomics
Research Field:Medical Biochemistry: Nucleic Acids
Objective Division:Health
Objective Group:Other Health
Objective Field:Health not elsewhere classified
Author:Dickinson, JL (Associate Professor Joanne Dickinson)
ID Code:13931
Year Published:1998
Web of Science® Times Cited:59
Deposited By:Menzies Centre
Deposited On:1998-08-01
Last Modified:2011-08-08
Downloads:0

Repository Staff Only: item control page