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Binding and Entry of 1918 Pandemic Influenza Receptor Binding Domain Variants in Normal Human Bronchial Epithelial Cells
Author(s) -
Davis A,
Chertow Daniel,
Qi Li,
Taubenberger Jeffery
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.507.4
Subject(s) - biology , hemagglutinin (influenza) , cell culture , virus , receptor , viral entry , influenza a virus , virology , glycoprotein , sialic acid , viral replication , microbiology and biotechnology , genetics
The 1918 “Spanish” influenza pandemic is the most severe influenza pandemic to date. Many questions remain regarding its origin, mechanisms of adaptation, and enhanced pathogenicity in humans. We used the human trachea derived primary cell line, normal human bronchial epithelial (NHBE) cells, to examine the binding and entry pattern of 5 1918 receptor binding domain variants: A/1/SC/1918 (SC), A/1/NY/1918 (NY), A/1/1918/VA (VA), A/1/1918/NY3 (NY3), and the ‘avianized’ 1918 virus. Prevailing hypotheses postulate that the hemagglutinin protein of avian‐adapted influenza viruses binds via a2,3 sialic acid (Sia)‐linked glycans and that the mammalian‐adapted viruses bind a2,6 Sia‐linked glycans, and that host switch requires a complete change in this Sia preference. SC exclusively binds and VA is predicted to bind a2,6, NY binds mixed a2,3/α2,6, NY3′s binding preference is unknown and the ‘avianized’ virus exclusively binds a2,3 Sia. We hypothesized that these viruses' binding and entry profiles would align with their Sia preferences as well as show a distinct cell type tropism correlating with the NHBE cells' Sia receptor distribution. We used immunofluorescence to analyze virus entry by epithelial cell type. Interestingly, all 5 viruses bound and entered the NHBE cells and AV was the most effective, easily entering both goblet and ciliated cells, including cells that express only a2,6 Sia on their surface. AV also grew to higher titers than NY and SC in an NHBE multi‐cycle replication kinetics study. NIH intramural research program.Confocal maximum projection images of NY3 infected NHBEs; influenza antigen (green), nuclei (gray), goblet (magenta) ciliated (red) and basal cells (blue). Bar 20 um.