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The Hemagglutinin: A Determinant of Pathogenicity

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Influenza Pathogenesis and Control - Volume I

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 385))

Abstract

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.

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Acknowledgments

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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  1. Institut für Virologie, Philipps-Universität, Hans-Meerwein-Str. 2, 35043, Marburg, Germany

    Eva Böttcher-Friebertshäuser, Wolfgang Garten, Mikhail Matrosovich & Hans Dieter Klenk

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  1. Eva Böttcher-Friebertshäuser
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  2. Wolfgang Garten
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  3. Mikhail Matrosovich
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  4. Hans Dieter Klenk
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Correspondence to Hans Dieter Klenk .

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  1. Department of Microbiology and Immunology, Emory University, Atlanta, Georgia, USA

    Richard W. Compans

  2. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA

    Michael B. A. Oldstone

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Böttcher-Friebertshäuser, E., Garten, W., Matrosovich, M., Klenk, H.D. (2014). The Hemagglutinin: A Determinant of Pathogenicity. In: Compans, R., Oldstone, M. (eds) Influenza Pathogenesis and Control - Volume I. Current Topics in Microbiology and Immunology, vol 385. Springer, Cham. https://doi.org/10.1007/82_2014_384

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