Modeling gene sequences over time in 2009 H1N1 influenza A virus populations.

BACKGROUND

A sudden emergence of Influenza A Virus (IAV) infections with a new pandemic H1N1 IAV is taking place since April of 2009. In order to gain insight into the mode of evolution of these new H1N1 strains, we performed a Bayesian coalescent Markov chain Monte Carlo (MCMC) analysis of full-length neuraminidase (NA) gene sequences of 62 H1N1 IAV strains (isolated from March 30th to by July 28th, 2009).

RESULTS

The results of these studies revealed that the expansion population growth model was the best to fit the sequence data. A mean of evolutionary change of 7.84 x 10(-3) nucleotide substitutions per site per year (s/s/y) was obtained for the NA gene. A significant contribution of first codon position to this mean rate was observed. Maximum clade credibility trees revealed a rapid diversification of NA genes in different genetic lineages, all of them containing Oseltamivir-resistant viruses of very recent emergence. Mapping of naturally occurring amino acid substitutions in the NA protein from 2009 H1N1 IAV circulating in 62 different patients revealed that substitutions are distributed all around the surface of the molecule, leaving the hydrophobic core and the catalytic site essentially untouched.

CONCLUSION

High evolutionary rates and fast population growth have contributed to the initial transmission dynamics of 2009 H1N1 IAV. Naturally occurring substitutions are preferentially located at the protein surface and do not interfere with the NA active site. Antigenic regions relevant for vaccine development can differ from previous vaccine strains and vary among patients.