title: The ability of pandemic influenza virus hemagglutinins to induce lower respiratory pathology is associated with decreased surfactant protein D binding.
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.
authors.affiliation: Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Qi
authors.forename: John C
authors.initials: JC
authors.lastname: Kash
authors.forename: Vivien G
authors.initials: VG
authors.lastname: Dugan
authors.forename: Brett W
authors.initials: BW
authors.lastname: Jagger
authors.forename: Yuk-Fai
authors.initials: YF
authors.lastname: Lau
authors.forename: Zhong-Mei
authors.initials: ZM
authors.lastname: Sheng
authors.forename: Erika C
authors.initials: EC
authors.lastname: Crouch
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
authors.forename: Jeffery K
authors.initials: JK
authors.lastname: Taubenberger
mesh_terms: D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000821:virology; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism*; D006651:Histocytochemistry; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity*; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008853:Microscopy; D011024:Pneumonia, Viral / Q000473:pathology*; D011485:Protein Binding; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism*; D016019:Survival Analysis; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D037663:Pulmonary Surfactant-Associated Protein D; D037521:Virulence Factors; C483468:hemagglutinin, human influenza A virus