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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 |
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Research Division: | Biomedical and Clinical Sciences |
Research Group: | Medical biochemistry and metabolomics |
Research Field: | Medical biochemistry - nucleic acids |
Objective Division: | Health |
Objective Group: | Other health |
Objective Field: | Other health not elsewhere classified |
UTAS Author: | Dickinson, JL (Professor Joanne Dickinson) |
ID Code: | 13931 |
Year Published: | 1998 |
Web of Science® Times Cited: | 67 |
Deposited By: | Menzies Centre |
Deposited On: | 1998-08-01 |
Last Modified: | 2011-08-08 |
Downloads: | 0 |
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