Infection of human airway epithelium by human and avian strains of influenza a virus.
We describe the characterization of influenza A virus infection of an established in vitro model of human pseudostratified mucociliary airway epithelium (HAE). Sialic acid receptors for both human and avian viruses, alpha-2,6- and alpha-2,3-linked sialic acids, respectively, were detected on the HAE cell surface, and their distribution accurately reflected that in human tracheobronchial tissue. Nonciliated cells present a higher proportion of alpha-2,6-linked sialic acid, while ciliated cells possess both sialic acid linkages. Although we found that human influenza viruses infected both ciliated and nonciliated cell types in the first round of infection, recent human H3N2 viruses infected a higher proportion of nonciliated cells in HAE than a 1968 pandemic-era human virus, which infected proportionally more ciliated cells. In contrast, avian influenza viruses exclusively infected ciliated cells. Although a broad-range neuraminidase abolished infection of HAE by human parainfluenza virus type 3, this treatment did not significantly affect infection by influenza viruses. All human viruses replicated efficiently in HAE, leading to accumulation of nascent virus released from the apical surface between 6 and 24 h postinfection with a low multiplicity of infection. Avian influenza A viruses also infected HAE, but spread was limited compared to that of human viruses. The nonciliated cell tropism of recent human H3N2 viruses reflects a preference for the sialic acid linkages displayed on these cell types and suggests a drift in the receptor binding phenotype of the H3 hemagglutinin protein as it evolves in humans away from its avian virus precursor.
Thompson
Catherine I
CI
Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27759-7248, USA.
Barclay
Wendy S
WS
Zambon
Maria C
MC
Pickles
Raymond J
RJ
D000818:Animals; D001717:Birds; D001980:Bronchi / Q000737:chemistry / Q000821:virology*; D002923:Cilia / Q000821:virology; D004848:Epithelium / Q000737:chemistry / Q000821:virology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000502:physiology*; D009980:Influenza A virus / Q000502:physiology*; D005585:Influenza in Birds / Q000821:virology*; D007251:Influenza, Human / Q000821:virology*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000032:analysis / Q000378:metabolism; D014132:Trachea / Q000737:chemistry / Q000821:virology*; D014779:Virus Replication
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011956:Receptors, Cell Surface; C109963:hemagglutinin, avian influenza A virus; C092488:sialic acid receptor; D019158:N-Acetylneuraminic Acid