title: Fatal cases of influenza A(H3N2) in children: insights from whole genome sequence analysis.
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.
authors.affiliation: Microbiology Services, Health Protection Agency, London, United Kingdom. Monica.Galiano@hpa.org.uk
authors.forename: Monica
authors.initials: M
authors.lastname: Galiano
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Johnson
authors.forename: Richard
authors.initials: R
authors.lastname: Myers
authors.forename: Joanna
authors.initials: J
authors.lastname: Ellis
authors.forename: Rod
authors.initials: R
authors.lastname: Daniels
authors.forename: Maria
authors.initials: M
authors.lastname: Zambon
mesh_terms: D019943:Amino Acid Substitution; D002648:Child; D016679:Genome, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D007251:Influenza, Human / Q000401:mortality* / Q000821:virology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010802:Phylogeny; D015995:Prevalence; D011487:Protein Conformation; D055503:Protein Multimerization; D016865:Reassortant Viruses / Q000235:genetics; D017422:Sequence Analysis, DNA; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus