Evolution and interspecies transmission of swine influenza viruses in China

Abstract

Pig plays important roles in the ecology and evolution of influenza A virus, by maintaining the diversity of viruses, and by accepting and transmitting viruses or virus genes from/to other species. The emergence of 2009 pandemic virus (pdm/09) indicated that this host could independently facilitate the genesis of a pandemic strain. Its repeated introductions back into pigs illustrated the two-way transmission nature of this virus. The occasional infection and adaption of avian influenza viruses (AIVs) in pig further reinforce the need to monitor the evolution and interspecies transmission of swine influenza viruses (SIVs). Based on the systematic surveillance system in southern China from 2009-2015, the epidemiology and evolution of SIVs have been elaborated, especially on the change of genotypic diversity and the establishment of different lineages. In addition, whole genomic sequences of the H3N2 human-origin SIVs isolated from our surveillance system since 1998 were combined with all the publicly available human and swine virus sequences to trace the longitudinal evolutionary dynamics of human seasonal H3N2 influenza virus in pigs globally. Genesis of the avian-origin SIVs in the study area was also explored. Phylogenetic analyses of the full genomic sequences of 1090 SIVs generated in our surveillance, together with reference sequences from public databases revealed the expansion of genotypic diversity in southern China and predominance of pdm/09- like internal genes. Repeated introductions of pdm/09 back into pigs did not lead to the establishment of this virus. Lineage establishment and replacement were observed, and their contributions to the diversity of SIVs were evaluated. Evolutionary analyses of the global human-origin H3 SIVs indicated that the frequent human-to-swine transmissions have led to the persistence of at least six major lineages in pigs. All of them harbored internal genes from enzootic SIV lineages, and maintained lowly glycosylated in the hemagglutinin globular head regions. Whole virus introductions into pigs occurred more frequently in early human viruses, which is consistent with their higher infectivity in ex vivo pig lung tissues. Different subtypes of avian-origin influenza viruses (H3N2, H5N1 and H9N2) were detected in pigs by our surveillance program. Their emerging pathways and molecular changes associated with the avian-to-swine transmission were depicted. Seroprevalence of an avian-origin H3N2 virus and its infectivity in pig lung explants were determined, suggesting a dead-end introduction of this virus. The role of landbased poultry in adapting AIVs to infect swine is also discussed. This thesis demonstrated the central role of pigs in the interspecies transmission of influenza A virus. Viruses from human and birds could add the genetic diversity of SIVs and the subsequent reassortment with their enzootic counterparts may further diversify the viral variety, from which potential pandemic or zoonotic strains might emerge. The continuous evolution of SIVs needs to be closely monitored for its threats to public health and pig industry.