Annexin II incorporated into influenza virus particles supports virus replication by converting plasminogen into plasmin.
For influenza viruses to become infectious, the proteolytic cleavage of hemagglutinin (HA) is essential. This usually is mediated by trypsin-like proteases in the respiratory tract. The binding of plasminogen to influenza virus A/WSN/33 leads to the 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. The inhibition of the conversion of plasminogen into plasmin blocked influenza virus replication. Evidence is provided that the activation of plasminogen is mediated by the host cellular protein annexin II, which is incorporated into the virus particles. Indeed, the inhibition of plasminogen binding to annexin II by using a competitive inhibitor inhibits plasminogen activation into plasmin. Collectively, these results indicate that the annexin II-mediated activation of plasminogen supports the replication of influenza viruses, which may contribute to their pathogenicity.
LeBouder
Fanny
F
Unité de Virologie et Immunologie Moléculaires, UR 892 INRA, Domaine de Vilvert, 78352 Jouy-en-Josas, France.
Morello
Eric
E
Rimmelzwaan
Guus F
GF
Bosse
Françoise
F
Péchoux
Christine
C
Delmas
Bernard
B
Riteau
Béatrice
B
D000818:Animals; D017306:Annexin A2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D004285:Dogs; D005341:Fibrinolysin / Q000378:metabolism*; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000254:growth & development; D053122:Influenza A Virus, H3N2 Subtype / Q000737:chemistry / Q000254:growth & development; D009980:Influenza A virus / Q000737:chemistry / Q000254:growth & development*; D010958:Plasminogen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011485:Protein Binding; D014779:Virus Replication / Q000502:physiology*
D017306:Annexin A2; D010958:Plasminogen; D005341:Fibrinolysin