Emergent 2009 influenza A(H1N1) viruses containing HA D222N mutation associated with severe clinical outcomes in the Americas

Huo Shu H. Houng*, Jason Garner, Yanfei Zhou, Arthur Lyons, Robert Kuschner, Gregory Deye, Kristina St. Clair, Richard W. Douce, Wilson Chicaiza, Patrick J. Blair, Christopher A. Myers, Ronald L. Burke, Jose L. Sanchez, Maya Williams, Eric S. Halsey

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Background: During the 2010-2011 influenza season, a small sub-group of 2009 influenza A(H1N1) viruses (hereafter referred to as 2009 A(H1N1)) emerged that was associated with more severe clinical outcomes in Ecuador and North America. Genetically, the haemagglutinin (HA) of this sub-clade was distinct from HAs found in viruses associated with severe outbreaks in 2010 from the United Kingdom and from other global specimens isolated earlier in the season. Objective: We report the emergence of a novel 2009 A(H1N1) variant possessing a re-emergent HA D222N mutation obtained from patients with severe respiratory illnesses and phylogenetically characterise these D222N mutants with other severe disease-causing variants clustering within a common emerging sub-clade. Case reports: In early 2011, three cases of 2009 A(H1N1) infection, two from Quito, Ecuador, and one from Washington, DC, USA, were complicated by severe pneumonia requiring mechanical ventilation, resulting in one fatality. These cases were selected due to the reported nature of the acute respiratory distress (ARD) that were captured in Department of Defence (DoD)-sponsored global influenza surveillance nets. Results: Genetically, the 2009 A(H1N1) strains isolated from two of the three severe cases carried a prominent amino acid change at position 222 (D222N) within the primary HA receptor binding site. Furthermore, these cases represent an emerging sub-clade of viruses defined by amino acid changes within HA: N31D, S162N, A186T and V272I. Phylogenetically, these viruses share a high degree of homology with strains associated with recent fatal cases in Chihuahua, Mexico. Discussion: Previously, enhanced virulence associated with the change, D222G, has been clinically linked to severe morbidity and mortality. Initial observations of the prevalence of a novel sub-clade of strains in the Americas suggest that viruses with a re-emergent D222N mutation may too correlate with severe clinical manifestations. These findings warrant heightened vigilance for emerging sub-clades of 2009 A(H1N1) and presumptive clinical implications.

Original languageEnglish
Pages (from-to)12-15
Number of pages4
JournalJournal of Clinical Virology
Issue number1
StatePublished - Jan 2012
Externally publishedYes


  • 2009 A(HINI)
  • D222N
  • HA receptor binding site
  • Influenza
  • Severe infections


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