Polymorphisms at residue 222 of the hemagglutinin of pandemic influenza A(H1N1)pdm09: association of quasi-species to morbidity and mortality in different risk categories

PLoS One. 2014 Mar 25;9(3):e92789. doi: 10.1371/journal.pone.0092789. eCollection 2014.

Abstract

The D222G substitution in the hemagglutinin (HA) gene of the pandemic influenza A(H1N1)pdm09 virus has been identified as a potential virulence marker, because this change allows for virus invasion deeper into the respiratory tract. In this study, we analyzed D, G and N polymorphisms at residue 222 by pyrosequencing (PSQ). We initially analyzed 401 samples from Brazilian patients. These were categorized with respect to clinical conditions due to influenza infection (mild, serious or fatal) and sub-stratified by risky factors. The frequency of mixed population of virus, with more than one polymorphism at residue 222, was significantly higher in serious (10.6%) and fatal (46.7%) influenza cases, whereas those who showed mild influenza infections were all infected by D222 wild-type. Mixtures of quasi-species showed a significant association of mortality, especially for those with risk factors, in special pregnant women. These results not only reinforce the association between D222G substitution and influenza A(H1N1)pdm09-associated morbidity and mortality, but also add the perspective that a worse clinical prognosis is most likely correlated with mixtures of quasi-species at this HA residue. Therefore, quasi-species may have a critical and underestimated role in influenza-related clinical outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics*
  • Humans
  • Influenza A Virus, H1N1 Subtype / genetics*
  • Influenza, Human* / genetics
  • Influenza, Human* / mortality
  • Male
  • Pandemics*
  • Polymorphism, Genetic*
  • Pregnancy
  • Pregnancy Complications, Infectious* / genetics
  • Pregnancy Complications, Infectious* / mortality
  • Risk Factors

Substances

  • H1N1 virus hemagglutinin
  • Hemagglutinin Glycoproteins, Influenza Virus

Grants and funding

Brazilian Ministry of Health and Ministry of Technology and Science, CNPq and FAPERJ provided funding to conduct this research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.