Plasminogen promotes influenza A virus replication through an annexin 2-dependent pathway in the absence of neuraminidase.
Proteolytic cleavage of haemagglutinin (HA) is essential for the infectivity of influenza A viruses (IAVs). This is usually mediated by trypsin-like proteases present in the respiratory tract. However, the ability to use plasminogen (PLG) as an alternative protease may contribute to pathogenesis of IAV infections and virus replication outside the respiratory tract. It was demonstrated previously that neuraminidase (NA) of the IAV strain A/WSN/33 can sequester PLG, allowing this virus to replicate in a PLG-dependent fashion. However, PLG also promotes replication of other IAVs, although its mode of action is poorly understood. Here, using NA-deficient viruses, we demonstrate that NA is not required for the binding of PLG and subsequent cleavage of HA. However, we demonstrate that the cellular protein annexin 2 (A2) can bind PLG and contributes to PLG-dependent cleavage of HA and subsequent IAV replication. Collectively, these results indicate that PLG promotes IAV replication in an A2-dependent fashion in the absence of NA.
LeBouder
Fanny
F
Unité de Virologie et Immunologie Moléculaires, UR 892 INRA, Domaine de Vilvert, F-78352 Jouy-en-Josas, France.
Lina
Bruno
B
Rimmelzwaan
Guus F
GF
Riteau
Béatrice
B
D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D009439:Neuraminidase / Q000172:deficiency*; D010958:Plasminogen / Q000378:metabolism*; D019562:Viral Load; D014764:Viral Proteins; D053586:Virus Internalization; D014779:Virus Replication
C472822:ANXA2 protein, human; D017306:Annexin A2; D014764:Viral Proteins; D010958:Plasminogen; C487630:NA protein, influenza A virus; D009439:Neuraminidase