The Hemagglutinin: A Determinant of Pathogenicity

  • Eva Böttcher-Friebertshäuser
  • Wolfgang Garten
  • Mikhail Matrosovich
  • Hans Dieter Klenk
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 385)


The hemagglutinin (HA) is a prime determinant of the pathogenicity of influenza A viruses. It initiates infection by binding to cell surface receptors and by inducing membrane fusion. The fusion capacity of HA depends on cleavage activation by host proteases, and it has long been known that highly pathogenic avian influenza viruses displaying a multibasic cleavage site differ in protease sensitivity from low pathogenic avian and mammalian influenza viruses with a monobasic cleavage site. Evidence is increasing that there are also variations in proteolytic activation among the viruses with a monobasic cleavage site, and several proteases have been identified recently that activate these viruses in a natural setting. Differences in protease sensitivity of HA and in tissue specificity of the enzymes are important determinants for virus tropism in the respiratory tract and for systemic spread of infection. Protease inhibitors that interfere with cleavage activation have the potential to be used for antiviral therapy and attenuated viruses have been generated by mutation of the cleavage site that can be used for the development of inactivated and live vaccines. It has long been known that human and avian influenza viruses differ in their specificity for sialic acid-containing cell receptors, and it is now clear that human tissues contain also receptors for avian viruses. Differences in receptor-binding specificity of seasonal and zoonotic viruses and differential expression of receptors for these viruses in the human respiratory tract account, at least partially, for the severity of disease. Receptor binding and fusion activation are modulated by HA glycosylation, and interaction of the glycans of HA with cellular lectins also affects virus infectivity. Interestingly, some of the mechanisms underlying pathogenicity are determinants of host range and transmissibility, as well.


Influenza Virus Avian Influenza Virus Human Virus Highly Pathogenic Avian Influenza Virus Human Influenza Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Sabine Fischbach for expert secretarial help. Research of the authors was supported by grants from the Deutsche Forschungsgemeinschaft (SFB 593, SFB 1021), the European Union 7th Framework Programme (278433 Predemics, 258084 FLUPIG), the Bundesministerium für Bildung und Forschung (FluResearchNet, DZIF), and the von Behring-Roentgen-Stiftung.


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Eva Böttcher-Friebertshäuser
    • 1
  • Wolfgang Garten
    • 1
  • Mikhail Matrosovich
    • 1
  • Hans Dieter Klenk
    • 1
  1. 1.Institut für VirologiePhilipps-UniversitätMarburgGermany

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