D225G mutation in hemagglutinin of pandemic influenza H1N1 (2009) virus enhances virulence in mice

  • Zheng B
  • Chan K
  • Zhang A
 et al. 
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Abstract

Although the majority of infections by the pandemic influenza H1N1 (2009) virus is mild, a higher mortality occurs in young adults with no risk factors for complications. Some of these severe cases were infected by the virus with an aspartate to glycine substitution at 225 position (D225G, H3 numbering) in the hemagglutinin (HA). Previous studies with the highly virulent 1918 pandemic H1N1 virus suggested that such substitution was associated with a dual binding specificity of the virus for both α2,3- and α2,6-linked sialic acid receptors on host cells. Thus, the D225G mutant may cause more severe disease with its increased predilection for the lower respiratory tract, where the α2,3 sialic acid receptor is more prevalent, but this hypothesis has not been investigated. We obtained a mutant virus after four sequential passages in lungs of BALB/c mice with a wild-type pandemic influenza A H1N1 (2009) virus. One plaque purified mutant virus had a single non-synonymous D225G mutation in the HA gene. This muta...

Author-supplied keywords

  • Adaptation
  • D222G
  • D225G
  • H1N1
  • Hemagglutinin
  • Influenza
  • Pandemic
  • Sialic acid

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