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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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Phylogenetic relationships of the concatenated main coding regions of influenza A(H3N2) viruses isolated in the UK during 2003–2004.Sequences from reference viruses A/Panama/2007/99 and A/Fujian/411/2002 were included in the dendrograms. For the purposes of comparison, the dendrograms also included sequences from A/New York/38/2003, A/New York/11/2003, A/New York/32/2003, A/New York/199/2003 and A/New York/52/2004. All phylogenies were rooted using A/Panama/2007/99 as an outgroup. Branch lengths are drawn to scale. Viruses isolated from fatal cases are displayed in red type. Bootstrap values (>70%) are displayed on the nodes. Genetic groups I and II are indicated with brackets. Amino acid substitutions characterising these groups are annotated on the nodes.
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pone-0033166-g001: Phylogenetic relationships of the concatenated main coding regions of influenza A(H3N2) viruses isolated in the UK during 2003–2004.Sequences from reference viruses A/Panama/2007/99 and A/Fujian/411/2002 were included in the dendrograms. For the purposes of comparison, the dendrograms also included sequences from A/New York/38/2003, A/New York/11/2003, A/New York/32/2003, A/New York/199/2003 and A/New York/52/2004. All phylogenies were rooted using A/Panama/2007/99 as an outgroup. Branch lengths are drawn to scale. Viruses isolated from fatal cases are displayed in red type. Bootstrap values (>70%) are displayed on the nodes. Genetic groups I and II are indicated with brackets. Amino acid substitutions characterising these groups are annotated on the nodes.

Mentions: A phylogenetic tree was inferred using the concatenated sequences of the main coding regions of 70 viruses (Figure 1 new). For the purpose of comparison, we also included genome sequences representing the main clusters seen in A(H3N2) viruses from New York during the season of 2003–2004 [10]. Virus sequences from the adult contacts of fatal case #6 were not included in the trees to avoid statistical bias. The analysis revealed that UK A(H3N2) viruses from 2003–2004 clustered within two genetic groups, named I and II. Two UK viruses, A/England/567/2003 and A/Scotland/78/2003 grouped in a single branch, external to both genetic groups I and II. A third minor genetic group (III) outgrouping all the others included a single UK strain, A/England/558/2003 (control case), together with A/Fujian/411/2002 and two viruses from New York, All viruses isolated from fatal cases were interspersed with control viruses within genetic groups I and II, with no evidence for clustering that could suggest genetic differences specific to the fatal cases viruses.


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 the concatenated main coding regions of influenza A(H3N2) viruses isolated in the UK during 2003–2004.Sequences from reference viruses A/Panama/2007/99 and A/Fujian/411/2002 were included in the dendrograms. For the purposes of comparison, the dendrograms also included sequences from A/New York/38/2003, A/New York/11/2003, A/New York/32/2003, A/New York/199/2003 and A/New York/52/2004. All phylogenies were rooted using A/Panama/2007/99 as an outgroup. Branch lengths are drawn to scale. Viruses isolated from fatal cases are displayed in red type. Bootstrap values (>70%) are displayed on the nodes. Genetic groups I and II are indicated with brackets. Amino acid substitutions characterising these groups are annotated on the nodes.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3295814&req=5

pone-0033166-g001: Phylogenetic relationships of the concatenated main coding regions of influenza A(H3N2) viruses isolated in the UK during 2003–2004.Sequences from reference viruses A/Panama/2007/99 and A/Fujian/411/2002 were included in the dendrograms. For the purposes of comparison, the dendrograms also included sequences from A/New York/38/2003, A/New York/11/2003, A/New York/32/2003, A/New York/199/2003 and A/New York/52/2004. All phylogenies were rooted using A/Panama/2007/99 as an outgroup. Branch lengths are drawn to scale. Viruses isolated from fatal cases are displayed in red type. Bootstrap values (>70%) are displayed on the nodes. Genetic groups I and II are indicated with brackets. Amino acid substitutions characterising these groups are annotated on the nodes.
Mentions: A phylogenetic tree was inferred using the concatenated sequences of the main coding regions of 70 viruses (Figure 1 new). For the purpose of comparison, we also included genome sequences representing the main clusters seen in A(H3N2) viruses from New York during the season of 2003–2004 [10]. Virus sequences from the adult contacts of fatal case #6 were not included in the trees to avoid statistical bias. The analysis revealed that UK A(H3N2) viruses from 2003–2004 clustered within two genetic groups, named I and II. Two UK viruses, A/England/567/2003 and A/Scotland/78/2003 grouped in a single branch, external to both genetic groups I and II. A third minor genetic group (III) outgrouping all the others included a single UK strain, A/England/558/2003 (control case), together with A/Fujian/411/2002 and two viruses from New York, All viruses isolated from fatal cases were interspersed with control viruses within genetic groups I and II, with no evidence for clustering that could suggest genetic differences specific to the fatal cases viruses.

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