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

Li Qi, John C. Kash, Vivien G. Dugan, Brett W. Jagger, Yuk Fai Lau, Zhong Mei Sheng, Erika C. Crouch, Kevan L. Hartshorn, Jeffery K. Taubenberger

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)426-434
Number of pages9
JournalVirology
Volume412
Issue number2
DOIs
StatePublished - Apr 10 2011

Keywords

  • Hemagglutinin
  • Influenza A virus
  • Mice
  • Pandemic
  • Pathology
  • Surfactant Protein D

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