Bayesian coalescent analysis of pandemic H1N1 influenza A virus circulating in the South American region

Virus Res. 2012 Dec;170(1-2):91-101. doi: 10.1016/j.virusres.2012.09.002. Epub 2012 Sep 13.

Abstract

The first influenza pandemic of this century was declared in April of 2009, with the emergence of a novel H1N1 influenza A virus strain (H1N1pdm). Understanding the evolution of H1N1pdm populations within the South American region is essential for studying global diversification, emergence, resistance and vaccine efficacy. In order to gain insight into these matters, we have performed a Bayesian coalescent Markov Chain Monte Carlo analysis of hemagglutinin (HA) and neuraminidase (NA) gene sequences of all available and comparable HA and NA sequences obtained from H1N1pdm IAV circulating in the South American region. High evolutionary rates and fast population growths characterize the population dynamics of H1N1pdm strains in this region of the world. A significant contribution of first codon position to the mean evolutionary rate was found for both genes studied, revealing a high contribution of non-synonymous substitutions to the mean substitution rate. In the 178days period covered by these studies, substitutions in all HA epitope regions can be observed. HA substitutions D239G/N and Q310H have been observed only in Brazilian patients. While substitution D239G/N is not particularly associated to a specific genetic lineage, all strains bearing substitution Q310H were assigned to clade 6, suggesting a founder effect. None of the substitutions found in the NA proteins of H1N1pdm strains isolated in South America appears sufficiently close to affect the drug binding pocket for the three NA inhibitor antivirals tested. A more detailed analysis of NA proteins revealed epitope differences among 2010 vaccine and H1N1pdm IAV strains circulating in the South American region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Bayes Theorem
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Humans
  • Influenza A Virus, H1N1 Subtype / classification
  • Influenza A Virus, H1N1 Subtype / genetics*
  • Influenza, Human / epidemiology*
  • Markov Chains
  • Models, Molecular
  • Monte Carlo Method
  • Neuraminidase / chemistry
  • Neuraminidase / genetics
  • Pandemics*
  • Phylogeny
  • Protein Conformation
  • South America / epidemiology

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • Neuraminidase