Picornavirus receptor down-regulation by plasminogen activator inhibitor type 2

Therapeutic interference with virus-cell surface receptor interactions repr esents a viable antiviral strategy. Here we demonstrate that cytoplasmic ex pression of the serine protease inhibitor (serpin), plasminogen activator i nhibitor type 2 (PAI-2), affords a high level of protection from lytic infe ction by multiple human picornaviruses. The antiviral action of PAI 2 was m ediated primarily through transcriptional down-regulation of the following virus receptors: intercellular adhesion molecule 1 (ICAM-1, a cellular rece ptor for the major group of rhinoviruses), decay-accelerating factor (a cel lular receptor for echoviruses and coxsackieviruses), and to a lesser exten t the coxsackie-adenovirus receptor protein (a cellular receptor for group B coxsackieviruses and group C adenoviruses). Expression of related cell su rface receptors, including membrane cofactor protein and the poliovirus rec eptor, remained unaffected. These findings suggest that PAI-2 and/or relate d serpins may form the basis of novel antiviral strategies against picornav irus infections and also therapeutic interventions against ICAM-1-mediated respiratory inflammation.