The ability of pandemic influenza virus hemagglutinins to induce lower respiratory pathology is associated with decreased surfactant protein D binding

Virology. 2011 Apr 10;412(2):426-34. doi: 10.1016/j.virol.2011.01.029. Epub 2011 Feb 18.


Pandemic influenza viral infections have been associated with viral pneumonia. Chimeric influenza viruses with the hemagglutinin segment of the 1918, 1957, 1968, or 2009 pandemic influenza viruses in the context of a seasonal H1N1 influenza genome were constructed to analyze the role of hemagglutinin (HA) in pathogenesis and cell tropism in a mouse model. We also explored whether there was an association between the ability of lung surfactant protein D (SP-D) to bind to the HA and the ability of the corresponding chimeric virus to infect bronchiolar and alveolar epithelial cells of the lower respiratory tract. Viruses expressing the hemagglutinin of pandemic viruses were associated with significant pathology in the lower respiratory tract, including acute inflammation, and showed low binding activity for SP-D. In contrast, the virus expressing the HA of a seasonal influenza strain induced only mild disease with little lung pathology in infected mice and exhibited strong in vitro binding to SP-D.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Body Weight
  • Disease Models, Animal
  • Epithelial Cells / virology
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism*
  • Histocytochemistry
  • Influenza A Virus, H1N1 Subtype / pathogenicity*
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Microscopy
  • Pneumonia, Viral / pathology*
  • Protein Binding
  • Pulmonary Surfactant-Associated Protein D / metabolism*
  • Survival Analysis
  • Virulence Factors / metabolism*


  • Hemagglutinin Glycoproteins, Influenza Virus
  • Pulmonary Surfactant-Associated Protein D
  • Virulence Factors
  • hemagglutinin, human influenza A virus