Influenza A viruses can infect a variety of birds and mammals. Its genome consists of 8 single-stranded RNA segments. The low proofreading activity of their polymerases and genomic rearrangements between different subtypes of influenza A viruses allow them to continuously evolve, which poses an ongoing threat to human and animal health. The 2009 influenza A virus pandemic highlighted the importance of the swine host in the adaptation of these viruses between humans and birds. The number of swine herds and the incidence of swine influenza A virus continue to grow. In previous studies, the growth and evolution of influenza A viruses despite vaccination was demonstrated in vaccinated and challenged pigs. However, how vaccination drives the evolutionary dynamics of swine influenza A viruses following co-infection with both subtypes has not been fully studied. In this study, vaccinated and unvaccinated pigs were challenged with direct contact with pigs vaccinated with swine influenza A viruses independent of H1N1 and H3N2. Nasal swab samples were collected daily, and bronchoalveolar lavage fluid from each pig was collected on the day of necropsy for influenza A virus detection and whole-genome sequencing. Through next-generation sequencing, a total of 39 complete genome sequences of swine influenza A viruses were obtained from samples collected by the two experimental groups. Subsequently, genomic and evolutionary analyzes were performed to detect genomic rearrangements and single nucleotide variations.
Regarding the fragments found in each sample, the presence of both isoforms was much lower in vaccinated animals, suggesting that the vaccine reduces the likelihood of genomic rearrangement events. Regarding intra-host diversity of swine influenza A viruses, 239 and 74 single-nucleotide variants were detected in the H1N1 and H3N2 subtypes, respectively. Different proportions of synonymous and non-synonymous substitutions were found, suggesting that the vaccine may be affecting major mechanisms of swine influenza A virus evolution, with natural, neutral and purifying selection detected in different analysis scenarios. Single nucleotide variants detected in the swine influenza A virus genome, with important nonsynonymous substitutions in the polymerase, surface glycoproteins, and nonstructural proteins, which may have consequences for viral replication, immune system evasion, and viral virulence influence, respectively.
This study further highlights the tremendous ability of swine influenza A viruses to evolve under natural infection and vaccine pressure.
López-Valiñas Á, Valle M, Wang M, Darji A, Cantero G, Chiapponi C, Segalés J, Ganges L, Núñez JI. Vaccination of pigs with swine influenza induces different patterns of drift evolution following experimental swine influenza virus infection and reduces the likelihood of genome reassortment. Frontiers in Cellular and Infectious Microbiology. 2023; 13. https://www.frontiersin.org/articles/10.3389/fcimb.2023.1111143