Plasminogen promotes influenza A virus replication through an annexin 2-dependent pathway in the absence of neuraminidase

F LeBouder, B Lina, Guus Rimmelzwaan, B Riteau

Research output: Contribution to journalArticleAcademicpeer-review

34 Citations (Scopus)


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.
Original languageUndefined/Unknown
Pages (from-to)2753-2761
Number of pages9
JournalJournal of General Virology
Publication statusPublished - 2010

Cite this