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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1 June 1998
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June 01 1998
The Serine Proteinase Inhibitor (Serpin) Plasminogen Activation Inhibitor Type 2 Protects against Viral Cytopathic Effects by Constitutive Interferon α/β Priming
Toni M. Antalis,
Toni M. Antalis
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
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May La Linn,
May La Linn
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
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Karen Donnan,
Karen Donnan
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
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Luis Mateo,
Luis Mateo
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
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Joy Gardner,
Joy Gardner
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
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Joanne L. Dickinson,
Joanne L. Dickinson
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
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Kathy Buttigieg,
Kathy Buttigieg
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
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Andreas Suhrbier
Andreas Suhrbier
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
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Toni M. Antalis
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
May La Linn
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
Karen Donnan
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
Luis Mateo
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
Joy Gardner
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
Joanne L. Dickinson
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
Kathy Buttigieg
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
Andreas Suhrbier
From the *Queensland Cancer Fund Experimental Oncology Unit and the ‡EBV Unit, The Queensland Institute of Medical Research, Brisbane 4029, Australia
Address correspondence to Toni M. Antalis, Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Brisbane 4029, Australia. Phone: 61-7-33620312; Fax 61-7-33620107; E-mail: [email protected]
Received:
July 17 1997
Revision Received:
February 27 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 187 (11): 1799–1811.
Article history
Received:
July 17 1997
Revision Received:
February 27 1998
Citation
Toni M. Antalis, May La Linn, Karen Donnan, Luis Mateo, Joy Gardner, Joanne L. Dickinson, Kathy Buttigieg, Andreas Suhrbier; The Serine Proteinase Inhibitor (Serpin) Plasminogen Activation Inhibitor Type 2 Protects against Viral Cytopathic Effects by Constitutive Interferon α/β Priming . J Exp Med 1 June 1998; 187 (11): 1799–1811. doi: https://doi.org/10.1084/jem.187.11.1799
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