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Swine influenza A viruses (swIAVs) can play a crucial role in the generation of new human pandemic viruses. In this study, in-depth passive surveillance comprising nearly 2,500 European swine holdings and more than 18,000 individual samples identified a year-round presence of up to four major swIAV lineages on more than 50% of farms surveilled. Phylogenetic analyses show that intensive reassortment with human pandemic A(H1N1)/2009 (H1pdm) virus produced an expanding and novel repertoire of at least 31 distinct swIAV genotypes and 12 distinct hemagglutinin/neuraminidase combinations with largely unknown consequences for virulence and host tropism. Several viral isolates were resistant to the human antiviral MxA protein, a prerequisite for zoonotic transmission and stable introduction into human populations. A pronounced antigenic variation was noted in swIAV, and several H1pdm lineages antigenically distinct from current seasonal human H1pdm co-circulate in swine. Thus, European swine populations represent reservoirs for emerging IAV strains with zoonotic and, possibly, pre-pandemic potential. • We observe a high incidence of influenza A virus in European swine populations • Lineages antigenically distinct from human vaccine strains were identified • Some isolates transmitted by aerosol in ferret models showed resistance to human MxA • European swine populations host building blocks of pre-pandemic influenza viruses Henritzi et al. detect in domestic pig populations in Europe Influenza A viruses with extended variability and antigenically distinct from human vaccine strains. Several isolates are resistant to human MxA and transmit by aerosol in ferrets. Building blocks of pre-pandemic influenza A viruses may be circulating in European swine populations. [ABSTRACT FROM AUTHOR] more...