The nonadaptive nature of the H1N1 2009 Swine Flu pandemic contrasts with the adaptive facilitation of transmission to a new host

Here we base our analysis on 1180 complete genomes of H1N1 viruses sampled in North America between 2000 and 2010 in swine and human hosts. We show that while transmission to a human host might require an adaptive phase in the HA and NA antigens, the emergence of the 2009 pandemic was essentially nonadaptive. A more detailed analysis of the NA protein shows that the 2009 pandemic sequence is characterized by novel epitopes and by a particular substitution in loop 150, which is responsible for a nonadaptive structural change tightly associated with the emergence of the pandemic.Because this substitution was not present in the 1918 H1N1 pandemic virus, we posit that the emergence of pandemics is due to epistatic interactions between sites distributed over different segments. Altogether, our results are consistent with population dynamics models that highlight the epistatic and nonadaptive rise of novel epitopes in viral populations, followed by their demise when the resulting virus is too virulent.Viruses are the cause of several deadly diseases such as yellow fever, dengue, hepatitis or seasonal Influenza. The etiologic agent of the latter, the Influenza virus, can cause mild to severe illnesses depending on the Influenza type and strain. The case of the 2009 H1N1 outbreak, first detected in humans in early 2009 [1], was caused by a antigenically novel strain that led the World Health Organization to declare the outbreak as the first Influenza pandemic of the 21st century. The emergence of such viruses in the human population has since attracted intense scrutiny, with a particular focus on two of their properties: virulence and interspecies transmission [2].The H1N1 virus is an Influenza A virus that belongs to the family of orthomyxoviruses, and has a segmented negative single-stranded RNA genome made of eight segments that each encode 1-2 proteins necessary for virus attachment to host cells and spread of viral infection. By approximate order of decreasing sizes, t