Vol.:(0123456789) 1 3 Archives of Virology (2018) 163:3035–3049 https://doi.org/10.1007/s00705-018-3962-z ORIGINAL ARTICLE Evolution and dynamics of the pandemic H1N1 infuenza hemagglutinin protein from 2009 to 2017 Hebah A. Al Khatib 1  · Asmaa A. Al Thani 2  · Hadi M. Yassine 2 Received: 17 May 2018 / Accepted: 31 July 2018 / Published online: 31 July 2018 © Springer-Verlag GmbH Austria, part of Springer Nature 2018 Abstract The emergence of swine-origin pandemic H1N1 (pH1N1) in 2009 invigorated extensive surveillance programs worldwide which have resulted in the deposition of large numbers of H1N1 sequences to Genbank. In the present study, we report on global evolution and dynamics of the pandemic H1N1 infuenza Hemagglutinin (HA) protein in viruses isolated from three diferent continents (North America, Europe and Asia) during the period between April 2009 until April 2017. Close to 2000 HA full protein sequences were downloaded from the Infuenza Research Database of the NCBI and analyzed using DNAStar to run an alignment, the web-based NetNglyc to predict N-Glycosylation sites and fnally, the BEAST software package to calculate evolution and substitution rates. Our analysis improves upon other published papers in that we report on frequencies, dynamics and impact of HA mutations in pH1N1 viruses isolated from three continents during the past decade, as well as the evolution rate and site-specifc selection pressures. Sequence based analysis demonstrated substantial changes in the HA protein over the last decade. Results showed that the HA gene is under negative selection (P value; HA= -2.253). The evolution rates varied among the three continents ranging from 2.36 × 10 −3 in Europe to 3.18 × 10 −3 in Asia. Mutations were detected at higher frequency and faster rate at the antigenic sites surrounding the receptor-binding domain (RBD), in particular, in the Sa and Sb sites. Mutations were either gradually accumulated to become fxed in currently circulating strains (D114N, S179N, S202T, S220T, I233T, K300E and E391K) or dynamic in terms of appearance and disappearance, both spatially and temporally (A203T, N458K and E508G). Some of the reported mutations have been shown to increase infection severity (D239G/N; globular head), enhance HA binding afnity to its receptor (S200P and S202T; RBD), or have deleterious efect on HA function (N458K and E508G; stem region). The continuous accumulation of mutations at the Sa site led to the gradual acquisition of glycosylation at residue 179 starting from 2015, which became a dominant feature in all strains isolated in the following years. In addition to sharing common amino acid substitutions (e.g. S179N in HA head and E516K in HA stem) with previous seasonal strains, the pattern of glycosylation acquisition/loss at 177 and 179 positions on the globular head, which are prominent features of immune escape, implicate that pH1N1 might follow a similar evolution trend as the SC1918 pandemic virus. Introduction Infuenza is the leading cause of respiratory illness world- wide. According to CDC estimations, infuenza has resulted in between 9.2 million and 60.8 million illnesses and between 12,000 and 56,000 deaths annually since 2010 [1]. Three major pandemics were reported in the last century: the 1918 Spanish infuenza caused by avian-origin H1N1 (SC1918) virus which killed around 20 million people [2], the 1957 Asian infuenza caused by reassortant H2N2 virus, and the 1968 Hong Kong infuenza caused by reassortant H3N2 virus. In April 2009, a novel H1N1 virus of swine ori- gin was detected in humans and quickly became pandemic and resulted in more than 600,000 laboratory confrmed Handling Editor: Hans Dieter Klenk. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00705-018-3962-z) contains supplementary material, which is available to authorized users. * Hadi M. Yassine Hyassine@qu.edu.qa 1 Biological and Biomedical Sciences Department, Hamad Bin Khalifah University, 34110 Doha, Qatar 2 Biomedical Research Center, Qatar University, 2713 Doha, Qatar