Activation of the Hemagglutinin of Influenza Viruses

  • Summer E. Galloway
  • Bo Liang
  • David A. SteinhauerEmail author


The hemagglutinin (HA) glycoprotein of influenza viruses is posttranslationally cleaved into the disulfide-linked subunits HA1 and HA2, and this proteolytic processing event is critical to the virus life cycle as it is required to activate membrane fusion potential and virus infectivity. High-resolution structures are available for the HA precursor (HA0), the cleaved neutral pH conformation of HA, and the low pH conformation that the HA assumes when triggered by acidification of endosomes to mediate fusion of viral and cellular membrane during virus entry. These structures have provided clues regarding the mechanisms by which proteolytic cleavage activates membrane fusion potential and how subsequent acidification drives the fusion process. It has been known for decades that influenza strains and subtypes can vary with regard to HA cleavage properties and that cleavage site sequences and the proteases that recognize them can represent a major determinant for virus pathogenicity. However, a number of questions remain with respect to the identity and characteristics of the proteases that activate HAs in the various natural hosts and complex ecosystems that constitute the realm of influenza viruses. The continuing study of HA cleavage properties and the proteases involved should illuminate our understanding not only of pathogenicity but other aspects of influenza biology including host range, transmission, and interplay with other microorganisms such as bacteria.


Influenza virus Hemagglutinin Activating proteases Membrane fusion pH optimum Pathogenesis 



The authors acknowledge the support by the US Department of Health and Human Services contract HHSN272201400004C (NIAID Centers of Excellence for Influenza Research and Surveillance).


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Summer E. Galloway
    • 1
  • Bo Liang
    • 2
  • David A. Steinhauer
    • 3
    Email author
  1. 1.Influenza Division, National Center for Immunization and Respiratory DiseasesCenters for Disease Control and PreventionAtlantaUSA
  2. 2.Department of Biochemistry, O. Wayne Rollins Research CenterEmory University School of MedicineAtlantaUSA
  3. 3.Department of Microbiology and Immunology, O. Wayne Rollins Research CenterEmory University School of MedicineAtlantaUSA

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