At present, there are H1N1, H1N2, and H3N2 major viral subtypes circulating among pigs worldwide. Among the swine H1N1 influenza lineages, the classical H1N1 swine (CS) lineage is related to the H1N1 virus that caused both the 1918 and 2009 human pandemics3,4. The Eurasian avian-like (EA) H1N1 viruses have been prevalent in European pigs since 19795 and had contributed its neuraminidase (NA) and matrix (M) segments to the H1N1/2009 pandemic virus6. In 1997–1998, double or triple-reassortant H3N2 strains emerged containing genes from classical swine H1N1, seasonal human, and avian viruses, and they became prevalent in swine in North America7–9. Following the outbreak of H1N1/2009 pandemic in humans, reassortant viruses derived from H1N1/2009 pandemic viruses and enzootic IAVs-S have been continuously detected from pigs in many regions globally10–19. Furthermore, sporadic human infection with EA H1N1 viruses and with EA-H1N1/2009 pandemic reassortant viruses has been reported20–23. Also, human infections with the swine-derived H3N2 variant (H3N2v) have been reported and they are associated with a IAV-S reassortant H3N2 strain that contains the M segment of the H1N1/2009 pandemic virus24, emphasizing the important role of pigs in the generation of reassortant influenza viruses with the potential to infect humans. Importantly, humans lack herd immunity to EA H1N1 viruses11,25, individuals aged ≤14 years show broad susceptibility against H3N2v viruses, and the seasonal human vaccine does not induce neutralizing antibodies against these IAVs-S26. The insufficient immunity in humans against H1 and H3 IAVs-S raises concerns over whether they could be the source of the next influenza pandemic.