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Journal of Virology, September 1999, p. 7193-7198, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Picornavirus Receptor Down-Regulation by Plasminogen Activator Inhibitor Type 2

D. R. Shafren,1,* J. Gardner,2 V. H. Mann,3 T. M. Antalis,3 and A. Suhrbier2

Picornaviral Research Unit, Discipline of Immunology and Microbiology, Faculty of Medicine and Health Sciences, University of Newcastle, Newcastle, New South Wales 2300,1 and Cellular Oncology Laboratory3 and Australian Centre for International & Tropical Health & Nutrition,2 Queensland Institute of Medical Research and University of Queensland, Brisbane, Queensland 4029, Australia

Received 4 February 1999/Accepted 21 May 1999

Therapeutic interference with virus-cell surface receptor interactions represents a viable antiviral strategy. Here we demonstrate that cytoplasmic expression of the serine protease inhibitor (serpin), plasminogen activator inhibitor type 2 (PAI-2), affords a high level of protection from lytic infection by multiple human picornaviruses. The antiviral action of PAI-2 was mediated primarily through transcriptional down-regulation of the following virus receptors: intercellular adhesion molecule 1 (ICAM-1, a cellular receptor for the major group of rhinoviruses), decay-accelerating factor (a cellular receptor for echoviruses and coxsackieviruses), and to a lesser extent the coxsackie-adenovirus receptor protein (a cellular receptor for group B coxsackieviruses and group C adenoviruses). Expression of related cell surface receptors, including membrane cofactor protein and the poliovirus receptor, remained unaffected. These findings suggest that PAI-2 and/or related serpins may form the basis of novel antiviral strategies against picornavirus infections and also therapeutic interventions against ICAM-1-mediated respiratory inflammation.

* Corresponding author. Mailing address: Picornaviral Research Unit, Discipline of Immunology and Microbiology, Faculty of Medicine and Health Sciences, University of Newcastle, Level 3, David Maddison Clinical Sciences Building, Royal Newcastle Hospital, Newcastle, New South Wales 2300, Australia. Phone: 61 2 4923 6158. Fax: 61 2 4923 6814. E-mail: dshafren{at}mail.newcastle.edu.au.

Journal of Virology, September 1999, p. 7193-7198, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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