Influenza A viruses originate in wild birds and are transmitted to other avian and mammalian species including humans. Pigs play an essential role in influenza virus ecology as they possess receptors for both avian and mammalian viruses, thus representing an ideal host for virus reassortment or adaptation. Often, viruses isolated from pigs contain genes from other species, a prime example being the 2009 H1N1 pandemic virus, which contained genetic material of avian, human and swine origin. However, it remains unknown what makes swine influenza viruses evolve into pandemic influenza viruses for humans. The scope of the EU-funded FLUPIG (Pathogenesis and transmission of influenza virus in pigs) project was to improve current knowledge on the viral genetic changes necessary for pandemic viruses. In this context, the consortium used a wide variety of ex vivo and animal models, including swine, to address this question. Researchers performed in vivo infection studies with avian H1N1 and H9N2 influenza viruses in pigs and studied their adaptation as well as their transmission capacity to other species. Pigs highly resembled humans with respect to the prevalence and distribution of avian and human influenza virus receptors in the airways. However, following attachment of the virus to the respective receptor, the stages of replication differed between avian and human viruses. To assess avian influenza virus adaptation, scientists performed serial passages in pigs to introduce mutations that make viruses more fit for replication in pigs. In addition, they generated a hybrid virus between the avian H9N2 and the 2009 pandemic H1N1 viruses. In both cases, the resultant virus exhibited a higher replication potential in pigs than the original avian virus. However, replication and transmission remained suboptimal when compared to that of fully swine adapted viruses, emphasizing the complexity of the virus adaptation process. Regarding immunity against pandemic influenza viruses, scientists found substantial cross-protection between antigenically distinct influenza viruses within a given HA subtype. However, cross-protection was limited between viruses with a different HA subtype. Collectively, the activities of the FLUPIG study provided fundamental knowledge on the adaptation and cross-species transmission of influenza virus. This has led to the design of novel attenuated influenza vaccines that target a diverse repertoire of viruses.
Influenza virus, transmission, H1N1, swine, H9N2, immunity