The Origin and Evolution of H1N1 Pandemic Influenza Viruses

Abstract

Despite extensive planning for the next influenza pandemic in humans, nature has once again confounded the influenza experts. The emergence and development of an H1N1 pandemic strain while an H1N1 virus was still circulating in humans is an unprecedented event. Here, we examine the emergence of H1N1 influenza viruses in the USA, Europe, and Asia from the natural aquatic bird reservoir through intermediate hosts including pigs and turkeys to humans. There were some remarkable parallel evolutionary developments in the swine influenza viruses in the Americas and in Eurasia. Classical swine influenza virus in the USA emerged either before or immediately after the Spanish influenza virus emerged in humans in 1918. Over the next 50 plus years this swine influenza virus became increasingly attenuated in pigs but occasionally transmitted to humans causing mild clinical infection but did not consistently spread human to human. The remarkable parallel evolution was the introduction of avian influenza virus genes independently in swine influenza viruses in Europe and the USA, with almost simultaneous acquisition of genes from seasonal human influenza. Influenza in pigs in both Eurasia and America became more aggressive necessitating the production of vaccines, and the incidence of transmission of clinical influenza to humans increased. Eventually the different triple reassortants with gene segments from avian, swine, and human influenza viruses in pigs in Europe and America met and mated and developed into the 2009 pandemic H1N1 influenza that is highly transmissible in people, pigs, and turkeys. Whether this occurred in Mexico or in Asia is currently unknown. The failure of the experts was to not recognize the importance of pigs in the evolution and host range transmission of influenza viruses with pandemic potential.