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Fatal cases of influenza A(H3N2) in children: insights from whole genome sequence analysis.

Galiano M, Johnson BF, Myers R, Ellis J, Daniels R, Zambon M - PLoS ONE (2012)

Bottom Line: During the Northern Hemisphere winter of 2003-2004 the emergence of a novel influenza antigenic variant, A/Fujian/411/2002-like(H3N2), was associated with an unusually high number of fatalities in children.No associated amino acid substitutions could be linked with an exclusive or higher occurrence in fatal cases.Host factors related to immune state and differences in genetic background between patients may also play important roles in determining the outcome of an influenza infection.

View Article: PubMed Central - PubMed

Affiliation: Microbiology Services, Health Protection Agency, London, United Kingdom. Monica.Galiano@hpa.org.uk

ABSTRACT
During the Northern Hemisphere winter of 2003-2004 the emergence of a novel influenza antigenic variant, A/Fujian/411/2002-like(H3N2), was associated with an unusually high number of fatalities in children. Seventeen fatal cases in the UK were laboratory confirmed for Fujian/411-like viruses. To look for phylogenetic patterns and genetic markers that might be associated with increased virulence, sequencing and phylogenetic analysis of the whole genomes of 63 viruses isolated from fatal cases and non fatal "control" cases was undertaken. The analysis revealed the circulation of two main genetic groups, I and II, both of which contained viruses from fatal cases. No associated amino acid substitutions could be linked with an exclusive or higher occurrence in fatal cases. The Fujian/411-like viruses in genetic groups I and II completely displaced other A(H3N2) viruses, but they disappeared after 2004. This study shows that two A(H3N2) virus genotypes circulated exclusively during the winter of 2003-2004 in the UK and caused an unusually high number of deaths in children. Host factors related to immune state and differences in genetic background between patients may also play important roles in determining the outcome of an influenza infection.

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Related in: MedlinePlus

Phylogenetic relationships of partial sequences (nucleotides 346 to 866) of the HA1 coding fragment for A(H3N2) viruses isolated in 2003–2004 in the UK and worldwide.Genetic groups where viruses from the UK clustered are highlighted in green (I) and red (II). Some branches were condensed for clarity purposes; adjacent legends indicate the country/region where the majority of viruses within a cluster were isolated and the number of viruses included. These clusters also included sporadic viruses from other countries which were not detailed. Sequences from reference viruses A/Panama/2007/99 and A/Fujian/411/2002 were included in the phylogeny. The ML phylogeny was rooted using A/Panama/2007/99 as an outgroup. Branch lengths are drawn to scale. Bootstrap values (>70%) are displayed on the nodes.
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pone-0033166-g004: Phylogenetic relationships of partial sequences (nucleotides 346 to 866) of the HA1 coding fragment for A(H3N2) viruses isolated in 2003–2004 in the UK and worldwide.Genetic groups where viruses from the UK clustered are highlighted in green (I) and red (II). Some branches were condensed for clarity purposes; adjacent legends indicate the country/region where the majority of viruses within a cluster were isolated and the number of viruses included. These clusters also included sporadic viruses from other countries which were not detailed. Sequences from reference viruses A/Panama/2007/99 and A/Fujian/411/2002 were included in the phylogeny. The ML phylogeny was rooted using A/Panama/2007/99 as an outgroup. Branch lengths are drawn to scale. Bootstrap values (>70%) are displayed on the nodes.

Mentions: The phylogenetic relationships in this dendrogram showed that there was clear evidence of geographical clustering, where most clusters showed predominance of viruses from the same region or neighbouring countries (Figure 4). However, in each cluster there were also sporadic viruses from other regions (not detailed in the figure). Genetic group I UK viruses formed part of a large cluster (highlighted in green) with a robust bootstrap value (80%) comprising 360 viruses from the rest of Europe (Austria, Finland and Denmark), North America (US) and Oceania (Australia and New Zealand). There were at least four subclusters within this group (condensed for clarity): i) US+UK viruses; ii) UK+Finland+Denmark; iii) Austria; iv) Australia+New Zealand. Genetic group I UK viruses were also represented in single branches within this large cluster.


Fatal cases of influenza A(H3N2) in children: insights from whole genome sequence analysis.

Galiano M, Johnson BF, Myers R, Ellis J, Daniels R, Zambon M - PLoS ONE (2012)

Phylogenetic relationships of partial sequences (nucleotides 346 to 866) of the HA1 coding fragment for A(H3N2) viruses isolated in 2003–2004 in the UK and worldwide.Genetic groups where viruses from the UK clustered are highlighted in green (I) and red (II). Some branches were condensed for clarity purposes; adjacent legends indicate the country/region where the majority of viruses within a cluster were isolated and the number of viruses included. These clusters also included sporadic viruses from other countries which were not detailed. Sequences from reference viruses A/Panama/2007/99 and A/Fujian/411/2002 were included in the phylogeny. The ML phylogeny was rooted using A/Panama/2007/99 as an outgroup. Branch lengths are drawn to scale. Bootstrap values (>70%) are displayed on the nodes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3295814&req=5

pone-0033166-g004: Phylogenetic relationships of partial sequences (nucleotides 346 to 866) of the HA1 coding fragment for A(H3N2) viruses isolated in 2003–2004 in the UK and worldwide.Genetic groups where viruses from the UK clustered are highlighted in green (I) and red (II). Some branches were condensed for clarity purposes; adjacent legends indicate the country/region where the majority of viruses within a cluster were isolated and the number of viruses included. These clusters also included sporadic viruses from other countries which were not detailed. Sequences from reference viruses A/Panama/2007/99 and A/Fujian/411/2002 were included in the phylogeny. The ML phylogeny was rooted using A/Panama/2007/99 as an outgroup. Branch lengths are drawn to scale. Bootstrap values (>70%) are displayed on the nodes.
Mentions: The phylogenetic relationships in this dendrogram showed that there was clear evidence of geographical clustering, where most clusters showed predominance of viruses from the same region or neighbouring countries (Figure 4). However, in each cluster there were also sporadic viruses from other regions (not detailed in the figure). Genetic group I UK viruses formed part of a large cluster (highlighted in green) with a robust bootstrap value (80%) comprising 360 viruses from the rest of Europe (Austria, Finland and Denmark), North America (US) and Oceania (Australia and New Zealand). There were at least four subclusters within this group (condensed for clarity): i) US+UK viruses; ii) UK+Finland+Denmark; iii) Austria; iv) Australia+New Zealand. Genetic group I UK viruses were also represented in single branches within this large cluster.

Bottom Line: During the Northern Hemisphere winter of 2003-2004 the emergence of a novel influenza antigenic variant, A/Fujian/411/2002-like(H3N2), was associated with an unusually high number of fatalities in children.No associated amino acid substitutions could be linked with an exclusive or higher occurrence in fatal cases.Host factors related to immune state and differences in genetic background between patients may also play important roles in determining the outcome of an influenza infection.

View Article: PubMed Central - PubMed

Affiliation: Microbiology Services, Health Protection Agency, London, United Kingdom. Monica.Galiano@hpa.org.uk

ABSTRACT
During the Northern Hemisphere winter of 2003-2004 the emergence of a novel influenza antigenic variant, A/Fujian/411/2002-like(H3N2), was associated with an unusually high number of fatalities in children. Seventeen fatal cases in the UK were laboratory confirmed for Fujian/411-like viruses. To look for phylogenetic patterns and genetic markers that might be associated with increased virulence, sequencing and phylogenetic analysis of the whole genomes of 63 viruses isolated from fatal cases and non fatal "control" cases was undertaken. The analysis revealed the circulation of two main genetic groups, I and II, both of which contained viruses from fatal cases. No associated amino acid substitutions could be linked with an exclusive or higher occurrence in fatal cases. The Fujian/411-like viruses in genetic groups I and II completely displaced other A(H3N2) viruses, but they disappeared after 2004. This study shows that two A(H3N2) virus genotypes circulated exclusively during the winter of 2003-2004 in the UK and caused an unusually high number of deaths in children. Host factors related to immune state and differences in genetic background between patients may also play important roles in determining the outcome of an influenza infection.

Show MeSH
Related in: MedlinePlus