tetano
Editor, Senior Moderator
[h=2]Highlights[/h]
? Amino acid D222N affects binding and replication of A(H1N1)pdm09 recombinant viruses.
? Viruses with D222N+S185N show tropism for ciliated and non-ciliated cells.
? Mutation S185N is a compensatory mutation to maintain viral fitness.
[h=2]Abstract[/h] We have analyzed the receptor binding profile of A(H1N1)pdm09 recombinant influenza viruses containing the amino acid substitution D222N which has been associated with a fatal case of infection. This mutation was investigated in conjunction with a secondary mutation, S185N. Using human tracheobronchial epithelial cells (HTBE), we found that single mutation D222N affects the binding and replication of the virus during initial stages of infection, with limited but preferred tropism to non-ciliated cells expressing α2,6-SA. However, in conjunction with the S185N change, the (D222N, S185N) virus shows a remarkable increase in binding and replication efficiency, with tropism for both ciliated and non-ciliated cells. Glycan microarray analysis demonstrated correlation between the binding profile and the cell tropism observed in the HTBE cells. These findings suggest that viruses with D222N required compensatory mutations such as S185N to maintain viral fitness, and in combination, affect the pathogenicity of the virus and the clinical outcome.
[h=2]Keywords[/h]
? Amino acid D222N affects binding and replication of A(H1N1)pdm09 recombinant viruses.
? Viruses with D222N+S185N show tropism for ciliated and non-ciliated cells.
? Mutation S185N is a compensatory mutation to maintain viral fitness.
[h=2]Abstract[/h] We have analyzed the receptor binding profile of A(H1N1)pdm09 recombinant influenza viruses containing the amino acid substitution D222N which has been associated with a fatal case of infection. This mutation was investigated in conjunction with a secondary mutation, S185N. Using human tracheobronchial epithelial cells (HTBE), we found that single mutation D222N affects the binding and replication of the virus during initial stages of infection, with limited but preferred tropism to non-ciliated cells expressing α2,6-SA. However, in conjunction with the S185N change, the (D222N, S185N) virus shows a remarkable increase in binding and replication efficiency, with tropism for both ciliated and non-ciliated cells. Glycan microarray analysis demonstrated correlation between the binding profile and the cell tropism observed in the HTBE cells. These findings suggest that viruses with D222N required compensatory mutations such as S185N to maintain viral fitness, and in combination, affect the pathogenicity of the virus and the clinical outcome.
[h=2]Keywords[/h]
- Influenza;
- Receptor;
- Binding;
- A(H1N1)pdm09;
- Mexico