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Continuous #evolution of #Eurasian #avian-like #H1N1 swine #influenza viruses with pdm/09-derived internal #genes enhances #pathogenicity in mice

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By G.M.

 


ABSTRACT

Swine influenza A virus (swIAV) is an important zoonotic pathogen with the potential to cause human influenza pandemics. Swine are considered “mixing vessels” for generating novel reassortant influenza A viruses. In 2009, a swine-origin reassortant virus (2009 pandemic H1N1, pdm/09 H1N1) spilled over to humans, causing a global influenza pandemic. This virus soon spread back into swine herds and reassorted with the circulating swIAVs. We previously reported that the genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bore pdm/09- and triple reassortant (TR)-derived internal genes, had been predominant in swine populations of China since 2016, posing a threat to both the swine industry and public health. Here, our ongoing surveillance confirmed that G4 EA H1N1 viruses remained the predominant swIAVs in China from 2019 to 2023 and had reassorted with the co-circulating swIAVs, such as the H3N2 virus, to generate novel reassortant EA H1N2 viruses. Genetic analyses revealed that the pdm/09-derived internal genes of G4 EA H1N1 viruses originated from reassortments between pdm/09 H1N1 and EA H1N1 viruses in 2009–2010 and underwent independent and continuous evolution in the swine host, exhibiting higher evolutionary rates than those of the pdm/09 H1N1 virus circulating in humans. The accelerated evolution of internal genes enhanced the polymerase activity of G4 EA H1N1 viruses in mammalian cells, resulting in increased viral replication and pathogenicity in mice. This study provides evidence for swine in promoting the genetic evolution of influenza A virus and highlights the need for increased attention to novel reassortant viruses in swine.


IMPORTANCE

The emergence of pdm/09 H1N1 virus highlights the role of swine influenza A viruses (swIAVs) in generating novel influenza viruses with pandemic potential. Since 2009, the pdm/09 H1N1 virus has been frequently transmitted to swine and reassorted with the circulating swIAVs, generating many new reassortant viruses bearing pdm/09-derived genes globally. The G4 EA H1N1 viruses, which bore pdm/09-derived internal genes and acquired increased human infectivity, remained the predominant swIAVs in China from 2019 to 2023 and reassorted with the co-circulating swIAVs to generate novel subtype viruses. The internal genes of G4 EA H1N1 viruses originated from the human pdm/09 H1N1 viruses during 2009–2010 and exhibited higher evolutionary rates and greater genetic diversity than those in the human host. This has contributed to increased viral adaptation and pathogenicity in mammals. Therefore, sustained surveillance and immunization efforts are essential to control emerging reassortant swIAVs and protect public health.

Source: Journal of Virology, https://journals.asm.org/doi/10.1128/jvi.00430-25

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