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Front Microbiol. 2018 Oct 31;9:2596. doi: 10.3389/fmicb.2018.02596. eCollection 2018.

Seasonal Genetic Drift of Human Influenza A Virus Quasispecies Revealed by Deep Sequencing.

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Viral Populations and Pathogenesis, Department of Virology, Institut Pasteur, Paris, France.
Molecular Genetics of RNA Viruses, Department of Virology, Institut Pasteur, Paris, France.
UMR 3569, Centre National de la Recherche Scientifique, Paris, France.
Cellule Pasteur, Université Paris Diderot-Université Sorbonne Paris Cité, Paris, France.
Bioinformatics and Biostatistics HUB, The Center of Bioinformatics, Biostatistics and Integrative Biology, Institut Pasteur, Paris, France.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.


After a pandemic wave in 2009 following their introduction in the human population, the H1N1pdm09 viruses replaced the previously circulating, pre-pandemic H1N1 virus and, along with H3N2 viruses, are now responsible for the seasonal influenza type A epidemics. So far, the evolutionary potential of influenza viruses has been mainly documented by consensus sequencing data. However, like other RNA viruses, influenza A viruses exist as a population of diverse, albeit related, viruses, or quasispecies. Interest in this quasispecies nature has increased with the development of next generation sequencing (NGS) technologies that allow a more in-depth study of the genetic variability. NGS deep sequencing methodologies were applied to determine the whole genome genetic heterogeneity of the three categories of influenza A viruses that circulated in humans between 2007 and 2012 in France, directly from clinical respiratory specimens. Mutation frequencies and single nucleotide polymorphisms were used for comparisons to address the level of natural intrinsic heterogeneity of influenza A viruses. Clear differences in single nucleotide polymorphism profiles between seasons for a given subtype also revealed the constant genetic drift that human influenza A virus quasispecies undergo.


NGS; genetic drift; influenza season; influenza virus; quasispecies

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