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Genetic diversity of the 2009 pandemic influenza A(H1N1) viruses in Finland.

Ikonen N, Haanpää M, Rönkkö E, Lyytikäinen O, Kuusi M, Ruutu P, Kallio-Kokko H, Mannonen L, Lappalainen M, Ziegler T, Julkunen I - PLoS ONE (2010)

Bottom Line: During the next three months almost all infections were found from patients who had recently traveled abroad.Most amino acid changes in HA and NA molecules accumulated on the surface of the molecule and were partly located in antigenic sites.All Finnish pandemic viruses were sensitive to oseltamivir having the amino acid histidine at residue 275 of the neuraminidase molecule.

View Article: PubMed Central - PubMed

Affiliation: Viral Infections Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare THL, Helsinki, Finland. niina.ikonen@thl.fi

ABSTRACT

Background: In Finland, the first infections caused by the 2009 pandemic influenza A(H1N1) virus were identified on May 10. During the next three months almost all infections were found from patients who had recently traveled abroad. In September 2009 the pandemic virus started to spread in the general population, leading to localized outbreaks and peak epidemic activity was reached during weeks 43-48.

Methods/results: The nucleotide sequences of the hemagglutinin (HA) and neuraminidase (NA) genes from viruses collected from 138 patients were determined. The analyzed viruses represented mild and severe infections and different geographic regions and time periods. Based on HA and NA gene sequences, the Finnish pandemic viruses clustered in four groups. Finnish epidemic viruses and A/California/07/2009 vaccine virus strain varied from 2-8 and 0-5 amino acids in HA and NA molecules, respectively, giving a respective maximal evolution speed of 1.4% and 1.1%. Most amino acid changes in HA and NA molecules accumulated on the surface of the molecule and were partly located in antigenic sites. Three severe infections were detected with a mutation at HA residue 222, in two viruses with a change D222G, and in one virus D222Y. Also viruses with change D222E were identified. All Finnish pandemic viruses were sensitive to oseltamivir having the amino acid histidine at residue 275 of the neuraminidase molecule.

Conclusions: The Finnish pandemic viruses were quite closely related to A/California/07/2009 vaccine virus. Neither in the HA nor in the NA were changes identified that may lead to the selection of a virus with increased epidemic potential or exceptionally high virulence. Continued laboratory-based surveillance of the 2009 pandemic influenza A(H1N1) is important in order to rapidly identify drug resistant viruses and/or virus variants with potential ability to cause severe forms of infection and an ability to circumvent vaccine-induced immunity.

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Amino acid differences in the HA between the Finnish pandemic viruses and the vaccine strain A/California/07/2009.A. The trimeric HA molecule with previously identified H1 protein-related antigenic sites (Sa in pink, Sb in blue, Ca1 in darker green, Ca2 in lighter green and Cb in orange) of influenza A(H1N1) viruses and with the receptor binding pocket (purple) is presented in side and from top view. Different monomers are shown in various shades of grey color. The structure is based on the 3-dimensional structure of A/South Carolina/1/18 (RCSB Protein bank accession number 1ruz) HA molecule, which is genetically the closest resolved H1 structure as compared to the 2009 pandemic H1 molecule. B. The amino acid differences between the HA molecules of the Finnish pandemic viruses and the A/California/07/2009 vaccine virus are shown in the trimeric HA structure. Amino acid changes in antigenic sites are colored as in panel A. Other changes (apart from antigenic sites) in the HA1 region are shown in yellow and in the HA2 region in gold. Changes in antigenic sites are illustrated by the amino acid residue number, the amino acids that have changed, and in addition, the number of viruses found to contain the respective amino acid (numbers in red denote severe infections).
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pone-0013329-g003: Amino acid differences in the HA between the Finnish pandemic viruses and the vaccine strain A/California/07/2009.A. The trimeric HA molecule with previously identified H1 protein-related antigenic sites (Sa in pink, Sb in blue, Ca1 in darker green, Ca2 in lighter green and Cb in orange) of influenza A(H1N1) viruses and with the receptor binding pocket (purple) is presented in side and from top view. Different monomers are shown in various shades of grey color. The structure is based on the 3-dimensional structure of A/South Carolina/1/18 (RCSB Protein bank accession number 1ruz) HA molecule, which is genetically the closest resolved H1 structure as compared to the 2009 pandemic H1 molecule. B. The amino acid differences between the HA molecules of the Finnish pandemic viruses and the A/California/07/2009 vaccine virus are shown in the trimeric HA structure. Amino acid changes in antigenic sites are colored as in panel A. Other changes (apart from antigenic sites) in the HA1 region are shown in yellow and in the HA2 region in gold. Changes in antigenic sites are illustrated by the amino acid residue number, the amino acids that have changed, and in addition, the number of viruses found to contain the respective amino acid (numbers in red denote severe infections).

Mentions: Figure 3 illustrates the amino acid changes between the Finnish pandemic viruses and the vaccine virus in a three-dimensional model of the HA molecule. Almost all amino acid changes on the HA molecule were located on the surface of the molecule. Some of the changes accumulated in antigenic sites, Ca1, Ca2, Cb, Sa and Sb [7] and these viruses were derived from patients suffering both mild or severe infections.


Genetic diversity of the 2009 pandemic influenza A(H1N1) viruses in Finland.

Ikonen N, Haanpää M, Rönkkö E, Lyytikäinen O, Kuusi M, Ruutu P, Kallio-Kokko H, Mannonen L, Lappalainen M, Ziegler T, Julkunen I - PLoS ONE (2010)

Amino acid differences in the HA between the Finnish pandemic viruses and the vaccine strain A/California/07/2009.A. The trimeric HA molecule with previously identified H1 protein-related antigenic sites (Sa in pink, Sb in blue, Ca1 in darker green, Ca2 in lighter green and Cb in orange) of influenza A(H1N1) viruses and with the receptor binding pocket (purple) is presented in side and from top view. Different monomers are shown in various shades of grey color. The structure is based on the 3-dimensional structure of A/South Carolina/1/18 (RCSB Protein bank accession number 1ruz) HA molecule, which is genetically the closest resolved H1 structure as compared to the 2009 pandemic H1 molecule. B. The amino acid differences between the HA molecules of the Finnish pandemic viruses and the A/California/07/2009 vaccine virus are shown in the trimeric HA structure. Amino acid changes in antigenic sites are colored as in panel A. Other changes (apart from antigenic sites) in the HA1 region are shown in yellow and in the HA2 region in gold. Changes in antigenic sites are illustrated by the amino acid residue number, the amino acids that have changed, and in addition, the number of viruses found to contain the respective amino acid (numbers in red denote severe infections).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2958116&req=5

pone-0013329-g003: Amino acid differences in the HA between the Finnish pandemic viruses and the vaccine strain A/California/07/2009.A. The trimeric HA molecule with previously identified H1 protein-related antigenic sites (Sa in pink, Sb in blue, Ca1 in darker green, Ca2 in lighter green and Cb in orange) of influenza A(H1N1) viruses and with the receptor binding pocket (purple) is presented in side and from top view. Different monomers are shown in various shades of grey color. The structure is based on the 3-dimensional structure of A/South Carolina/1/18 (RCSB Protein bank accession number 1ruz) HA molecule, which is genetically the closest resolved H1 structure as compared to the 2009 pandemic H1 molecule. B. The amino acid differences between the HA molecules of the Finnish pandemic viruses and the A/California/07/2009 vaccine virus are shown in the trimeric HA structure. Amino acid changes in antigenic sites are colored as in panel A. Other changes (apart from antigenic sites) in the HA1 region are shown in yellow and in the HA2 region in gold. Changes in antigenic sites are illustrated by the amino acid residue number, the amino acids that have changed, and in addition, the number of viruses found to contain the respective amino acid (numbers in red denote severe infections).
Mentions: Figure 3 illustrates the amino acid changes between the Finnish pandemic viruses and the vaccine virus in a three-dimensional model of the HA molecule. Almost all amino acid changes on the HA molecule were located on the surface of the molecule. Some of the changes accumulated in antigenic sites, Ca1, Ca2, Cb, Sa and Sb [7] and these viruses were derived from patients suffering both mild or severe infections.

Bottom Line: During the next three months almost all infections were found from patients who had recently traveled abroad.Most amino acid changes in HA and NA molecules accumulated on the surface of the molecule and were partly located in antigenic sites.All Finnish pandemic viruses were sensitive to oseltamivir having the amino acid histidine at residue 275 of the neuraminidase molecule.

View Article: PubMed Central - PubMed

Affiliation: Viral Infections Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare THL, Helsinki, Finland. niina.ikonen@thl.fi

ABSTRACT

Background: In Finland, the first infections caused by the 2009 pandemic influenza A(H1N1) virus were identified on May 10. During the next three months almost all infections were found from patients who had recently traveled abroad. In September 2009 the pandemic virus started to spread in the general population, leading to localized outbreaks and peak epidemic activity was reached during weeks 43-48.

Methods/results: The nucleotide sequences of the hemagglutinin (HA) and neuraminidase (NA) genes from viruses collected from 138 patients were determined. The analyzed viruses represented mild and severe infections and different geographic regions and time periods. Based on HA and NA gene sequences, the Finnish pandemic viruses clustered in four groups. Finnish epidemic viruses and A/California/07/2009 vaccine virus strain varied from 2-8 and 0-5 amino acids in HA and NA molecules, respectively, giving a respective maximal evolution speed of 1.4% and 1.1%. Most amino acid changes in HA and NA molecules accumulated on the surface of the molecule and were partly located in antigenic sites. Three severe infections were detected with a mutation at HA residue 222, in two viruses with a change D222G, and in one virus D222Y. Also viruses with change D222E were identified. All Finnish pandemic viruses were sensitive to oseltamivir having the amino acid histidine at residue 275 of the neuraminidase molecule.

Conclusions: The Finnish pandemic viruses were quite closely related to A/California/07/2009 vaccine virus. Neither in the HA nor in the NA were changes identified that may lead to the selection of a virus with increased epidemic potential or exceptionally high virulence. Continued laboratory-based surveillance of the 2009 pandemic influenza A(H1N1) is important in order to rapidly identify drug resistant viruses and/or virus variants with potential ability to cause severe forms of infection and an ability to circumvent vaccine-induced immunity.

Show MeSH
Related in: MedlinePlus