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J. Virol. doi:10.1128/JVI.00246-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Annexin II incorporated into influenza virus particles supports virus replication by converting plasminogen into plasmin

Unité de Virologie et Immunologie Moléculaires, UR 892 INRA, Domaine de Vilvert, 78352 Jouy-en-Josas, France; Department of Virology and Postgraduate School of Molecular Medicine, Erasmus Medical Center, Rotterdam, the Netherlands; Unité UR1196 Génomique et Physiologie de la Lactation, INRA, Plateau de Microscopie Electronique, 78352 Jouy-en-Josas cedex, France

^* To whom correspondence should be addressed. Email: beatrice.riteau{at}jouy.inra.fr.

	Abstract

For influenza viruses to become infectious, proteolytic cleavage of the hemagglutinin is essential. This is usually mediated by trypsin-like proteases in the respiratory tract. Binding of plasminogen to influenza virus A/WSN/33 leads to cleavage of HA, a feature determining its pathogenicity and neurotropism in mice. Here, we demonstrate that plasminogen also promotes the replication of other influenza virus strains. Inhibition of the conversion of plasminogen into plasmin blocked influenza virus replication. Evidence is provided that activation of plasminogen is mediated by the host cellular protein annexin-2, which is incorporated into the virus particles. Indeed, inhibition of plasminogen binding to annexin-2, using a competitive inhibitor, inhibits plasminogen activation into plasmin. Collectively, these results indicate that annexin-2-mediated activation of plasminogen supports the replication of influenza viruses, which may contribute to their pathogenicity.