Picornavirus receptor down-regulation by plasminogen activator inhibitor type 2.
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.
Shafren
D R
DR
Picornaviral Research Unit, Discipline of Immunology and Microbiology, Faculty of Medicine and Health Sciences, University of Newcastle, Newcastle, New South Wales 2300, Australia. dshafren@mail.newcastle.edu.au
Gardner
J
J
Mann
V H
VH
Antalis
T M
TM
Suhrbier
A
A
D018958:CD55 Antigens / Q000096:biosynthesis / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D015536:Down-Regulation; D004770:Enterovirus / Q000378:metabolism / Q000472:pathogenicity; D029822:Enterovirus B, Human / Q000378:metabolism / Q000472:pathogenicity; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000378:metabolism; D008565:Membrane Proteins; D010849:Picornaviridae / Q000378:metabolism* / Q000472:pathogenicity; D017396:Plasminogen Activator Inhibitor 2 / Q000235:genetics / Q000378:metabolism*; D017955:Poliovirus / Q000378:metabolism / Q000472:pathogenicity; D011991:Receptors, Virus / Q000096:biosynthesis / Q000378:metabolism*; D014158:Transcription, Genetic
D018958:CD55 Antigens; C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D008565:Membrane Proteins; D017396:Plasminogen Activator Inhibitor 2; D011991:Receptors, Virus; C066100:poliovirus receptor; D018799:Intercellular Adhesion Molecule-1