gms | German Medical Science

International Conference on SARS - one year after the (first) outbreak

08. - 11.05.2004, Lübeck

Determinants of influenza pathogenesis in birds and mammals


  • corresponding author presenting/speaker Hans-Dieter Klenk - Institut für Virologie, Philipps-Universität Marburg,
  • Gülsah Mehmetoglu - Institut für Virologie, Philipps-Universität Marburg,
  • Jürgen Stech - Institut für Virologie, Philipps-Universität Marburg,
  • Anke Feldmann - Institut für Virologie, Philipps-Universität Marburg,
  • Ralf Wagner - Institut für Virologie, Philipps-Universität Marburg,
  • Tatyana Matrosovich - Institut für Virologie, Philipps-Universität Marburg,
  • Mikhail Matrosovich - Institut für Virologie, Philipps-Universität Marburg,

International Conference on SARS - one year after the (first) outbreak. Lübeck, 08.-11.05.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04sars7.03

The electronic version of this article is the complete one and can be found online at:

Published: May 26, 2004

© 2004 Klenk et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Influenza viruses have a wide host range comprising mammals and many birds. It is generally assumed that human viruses responsible for world-wide pandemics with millions of deaths originate from avian reservoirs. Most influenza viruses cause local infection that is confined to the respiratory tract or, in the case of some avian strains, to the gut. In contrast, several avian strains belonging to subtypes H5 and H7 cause generalized infection. These highly pathogenic viruses, also called fowl plague viruses (FPV), are a major threat to the poultry industry. There is increasing evidence that FPV's may also be transmitted to humans und that their pathogenetic potential is preserved in the new host. To analyse the factors determining host range and pathogenicity we have investigated a series of H7 viruses that had been derived from a seal isolate by sequential passages first in chicken embryo cells and then in mice there by acquiring pathogenicity for the new host. Confirming a well established concept cleavage activation of the viral hemagglutinin by the ubiquitous cellular protease furin was found to be the prime factor responsible for the pathogenicity for chickens. Mouse adaptation, on the other hand, was the result of mutations in the viral polymerase complex that caused enhanced activity in mammalian cells. In two other studies we have analysed the cell tropism of human and avian influenza viruses in vascular and respiratory tissues. Studies in chick embryos revealed that infection with FPV is confined to endothelial cells. Endotheliotropism is determined, on one hand, by the high cleavability of HA that mediates virus entry into the vascular system and, on the other hand, by restricted receptor expression and polar budding that prevent spread of infection into tissues surrounding endothelia. Using cultures of differentiated human airway epithelial cells we found that human viruses infected mainly non-ciliated cells, whereas avian viruses showed a specificity for ciliated cells. This pattern correlated with the predominant localization of receptors for human viruses (2-6-linked neuraminic acid) on non-ciliated and receptors for avian viruses (2-3-linked neuraminic acid) on ciliated cells. We have thus identified the entry site of avian influenza viruses into the human respiratory tract and show that it is different from the replication site of human viruses. Taken together, our data indicate that cleavage activation and receptor specificity of the hemagglutinin and the interplay of the viral polymerase with yet unknown host factors are prime determinants of the host tropism and the pathogenicity of influenza viruses.