The ecology and evolution of swine influenza viruses in southern China after the 2009 H1N1 pandemic

Abstract

Domestic pig is an important mammalian host species of influenza A virus. The two-way transmissions of influenza viruses between human and swine have played important roles in shaping current influenza ecosystem, which directly resulted in the genesis of the 2009 H1N1 pandemic virus (pdm/09). After occurrence of the pandemic, the pdm/09-like H1N1 viruses have been repeatedly introduced into swine populations in many countries and subsequently generated many novel variants of swine influenza viruses (SIV) through reassortments with those existing enzootic SIV lineages. Using the findings of our ongoing swine influenza surveillance in southern China from 2009 to 2012, changes of the prevalence, evolution of SIVs in the region have been systematically investigated by full-genomic sequencing of all swine influenza isolates obtained in this survey period. The establishment and evolution of novel reassortant SIVs were investigated by phylogenetic analyses. Furthermore, changes of the N-linked glycosylation sites (NLGS) in the hemmaglutinin (HA) globular domain, which are important for immune evasion, were comparatively examined in the evolution of human and swine influenza viruses to study the different evolutionary patterns of influenza viruses in these two hosts. The complete genomes of 387 SIVs obtained in this survey revealed 17 reassortant genotypes with pdm/09-origin genes. Even though the entire pdm/09 virus and its surface genes cannot persist, its internal genes have become established and are now the predominant lineages in pigs in southern China. The major persistent pdm/09-origin reassortant forms contained at least five pdm/09-origin internal genes, and their surface genes were primarily of enzootic SIV origin. The pdm/09-origin internal genes are possibly in the process of replacing the local European avian-like or American triple-reassortant-like internal genes. These findings represent a marked change in the evolutionary patterns and the dramatical increase of genetic diversity of SIVs in China. The variations of NLGS in the globular domain of HA have been systematically studied along with the evolution of influenza viruses in human and swine, by using publicly available datasets. The number of NLGS gradually increased in the evolution of seasonal influenza viruses circulating in humans, while no or very little variation has occurred in the evolution of SIVs. During interspecies transmission of influenza virus from human to swine, NLGS near the receptor binding sites were often lost in most cases, especially for those over-glycosylated HAs. This study has revealed distinct evolutionary patterns of NLGS in human and swine influenza viruses, possibly associating with different selection pressures in these two hosts. This thesis has demonstrated the great impact of repeated introductions of pdm/09 viruses on the ecology and evolution of SIVs in southern China, and showed important molecular changes during the interspecies transmissions of influenza viruses from human to swine. Pigs were proposed to be a recipient of some human-origin influenza viruses, which provide an environment for reversing the biological properties (e.g. antigenicity and NLGS) of a human-adaptive virus and facilitating extensive reassortments with other porcine viruses circulating in swine, thus posing continuous threats to public health.