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The influenza A(H1N1)pdm2009 (H1N1/2009) virus that emerged in humans during March and early April 2009 in the Americas spread rapidly among humans to develop into the first human influenza pandemic in over 40 years123,000 global deaths from March to December 2009 were potentially associated with H1N1/2009 infection, with a greater mortality impact observed in parts of the Americas compared with Europe and Australia.

The emergence and circulation of H1N1/2009 virus contradicted prevailing theories at the time of pandemic emergence, wherein it was thought that a heterologous haemagglutinin (HA) subtype was required to initiate a new pandemic had sufficient genetic and antigenic differentiation between the emergent strains and circulating human seasonal H1N1 viruses to cause a pandemic.

To address this we analyse 3,000 H1N1/2009 genomes, including 214 full genomes generated from our surveillance in Singapore, in conjunction with antigenic data.

Here we show that natural selection acting on H1N1/2009 directly after introduction into humans was driven by adaptation to the new host.

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