Sweep Dynamics (SD) plots: Computational identification of selective sweeps to monitor the adaptation of influenza A viruses

Thorsten R. Klingen, Susanne Reimering, Jens Loers, Kyra Mooren, Frank Klawonn, Thomas Krey, Gülsah Gabriel, Alice C. McHardy
2018 Scientific Reports  
Monitoring changes in influenza A virus genomes is crucial to understand its rapid evolution and adaptation to changing conditions e.g. establishment within novel host species. Selective sweeps represent a rapid mode of adaptation and are typically observed in human influenza A viruses. We describe Sweep Dynamics (SD) plots, a computational method combining phylogenetic algorithms with statistical techniques to characterize the molecular adaptation of rapidly evolving viruses from longitudinal
more » ... equence data. SD plots facilitate the identification of selective sweeps, the time periods in which these occurred and associated changes providing a selective advantage to the virus. We studied the past genome-wide adaptation of the 2009 pandemic H1N1 influenza A (pH1N1) and seasonal H3N2 influenza A (sH3N2) viruses. The pH1N1 influenza virus showed simultaneous amino acid changes in various proteins, particularly in seasons of high pH1N1 activity. Partially, these changes resulted in functional alterations facilitating sustained humanto-human transmission. In the evolution of sH3N2 influenza viruses, we detected changes characterizing vaccine strains, which were occasionally revealed in selective sweeps one season prior to the WHO recommendation. Taken together, SD plots allow monitoring and characterizing the adaptive evolution of influenza A viruses by identifying selective sweeps and their associated signatures. Influenza A viruses are rapidly evolving pathogens causing respiratory infections with high morbidity and mortality in the human population 1 . Annual influenza epidemics result in 3 to 5 million reported infections and up to 250,000-500,000 cases of death 1 . Currently, the viral subtypes sH3N2 and pH1N1 are circulating in the human population. The H3N2 virus was introduced into the human population in 1968 and is endemic ever since. The swine-origin H1N1 subtype emerged in the 2009 influenza pandemic and was subsequently referred to as the 2009 pH1N1 virus. It replaced the formerly circulating seasonal H1N1 subtype 2,3 . The negative-sense RNA genome consists of eight segments that encode for 14 viral proteins 4 . A constant arms-race between the human immune system and the virus results in continuous adaptation of the viral genome. These changes facilitate the virus to escape the host's immune response elicited through vaccination or previous influenza infections 5 . Alterations in the major glycoproteins − hemagglutinin (HA) and neuraminidase (NA) − and genomic reassortment that change the viral antigenicity are defined as antigenic drift and result in re-occurring epidemics of seasonal influenza viruses 6 . Continuous antigenic changes of circulating strains require a re-evaluation of antigenically predominant strains by the WHO twice a year at the end of each season, leading to a recommendation for the vaccine composition for the following year 7-9 . The establishment of an antigenically new virus strain into an immunologically naive human population causes pandemics, mostly due to alterations in the receptor binding protein HA 10 . Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 ScIentIfIc RepoRTS | (2018) 8:373 |
doi:10.1038/s41598-017-18791-z pmid:29321538 pmcid:PMC5762865 fatcat:zi63v2xqcng4jjpeprgvjpjz6y