Journal Article

The genomic and epidemiological dynamics of human influenza A virus

Pybus, Oliver G., Nelson, Martha I., Holmes, Edward C., Rambaut, Andrew, Viboud, Cecile, Taubenberger, Jeffery K.

2008

Overview

The evolutionary interaction between influenza A virus and the human immune system, manifest as ‘antigenic drift’ of the viral haemagglutinin, is one of the best described patterns in molecular evolution. However, little is known about the genome-scale evolutionary dynamics of this pathogen. Similarly, how genomic processes relate to global influenza epidemiology, in which the A/H3N2 and A/H1N1 subtypes co-circulate, is poorly understood. Here through an analysis of 1,302 complete viral genomes sampled from temperate populations in both hemispheres, we show that the genomic evolution of influenza A virus is characterized by a complex interplay between frequent reassortment and periodic selective sweeps. The A/H3N2 and A/H1N1 subtypes exhibit different evolutionary dynamics, with diverse lineages circulating in A/H1N1, indicative of weaker antigenic drift. These results suggest a sink–source model of viral ecology in which new lineages are seeded from a persistent influenza reservoir, which we hypothesize to be located in the tropics, to sink populations in temperate regions. A tropical origin for flu virus The current debate in the United States on the selection of strains for the influenza vaccine highlights the need for epidemiological understanding of the influenza virus. An analysis of genome sequences from over 1,300 influenza A virus isolates from around the world shows that its evolution is characterized by a combination of frequent gene reassortment and occasionally strong selection. At the epidemiological level, the H3N2 and H1N1 virus subtypes exhibit dynamics suggestive of an ecological model in which new antigenic variants emerge periodically from a persistent influenza reservoir, perhaps in the tropics, to the sink populations in temperate regions. Current debate on the selection of strains for the influenza vaccine highlights the need for epidemiological understanding of human influenza A virus. This paper analyses genomic sequences from global viral isolates, and hypothesizes that the virus follows a 'sink-source' model, where new lineages keep arising from some areas and dying out in other areas.

• Publisher: Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
• Subject: Amino acids / Analysis / Avian influenza viruses / Biological and medical sciences / Comparative studies / Control / Dosage and administration / Epidemics / Epidemiologic methods / Epidemiology / Evolution, Molecular / General aspects / Genetic aspects / Genetic diversity / Genetic Drift / Genetic Variation / Genome, Viral - genetics / Genomics / Hemagglutinin Glycoproteins, Influenza Virus - genetics / Humanities and Social Sciences / Humans / Immune system / Influenza / Influenza A virus / Influenza A Virus, H1N1 Subtype - genetics / Influenza A Virus, H1N1 Subtype - immunology / Influenza A Virus, H3N2 Subtype - genetics / Influenza A Virus, H3N2 Subtype - immunology / Influenza vaccines / Influenza viruses / Influenza, Human - epidemiology / Influenza, Human - virology / Medical sciences / Models, Biological / Mortality / multidisciplinary / Natural history / Neuraminidase - genetics / New York - epidemiology / New Zealand - epidemiology / Phylogeny / Proteins / Reassortant Viruses - genetics / Reassortant Viruses - immunology / Science / Science (multidisciplinary) / Tropical environments / Viral genetics / Winter