Abstract
BackgroundH9N2 influenza viruses continuously circulate in multiple avian species and are repeatedly transmitted to humans, posing a significant threat to public health. To investigate the adaptation ability of H9N2 avian influenza viruses (AIVs) to mammals and the mutations related to the host switch events, we serially passaged in mice two H9N2 viruses of different HA lineages — A/Quail/Hong Kong/G1/97 (G1) of the G1-like lineage and A/chicken/Shandong/ZB/2007 (ZB) of the BJ/94-like lineage —and generated two mouse-adapted H9N2 viruses (G1-MA and ZB-MA) that possessed significantly higher virulence than the wide-type viruses.FindingZB-MA replicated systemically in mice. Genomic sequence alignment revealed 10 amino acid mutations coded by 4 different gene segments (PB2, PA, HA, and M) in G1-MA compared with the G1 virus and 23 amino acid mutations in 5 gene segments (PB1, PA, HA, M, and NS) in ZB-MA compared to ZB virus, indicating that the mutations in the polymerase, HA, M, and NS genes play critical roles in the adaptation of H9N2 AIVs to mammals, especially, the mutations of M1-Q198H and M1-A239T were shared in G1-MA and ZB-MA viruses. Additionally, several substitutions showed a higher frequency in human influenza viruses compared with avian viruses.ConclusionsDifferent lineages of H9N2 could adapt well in mice and some viruses could gain the ability to replicate systemically and become neurovirulent. Thus, it is essential to pay attention to the mammalian adaptive evolution of the H9N2 virus.
Highlights
H9N2 avian influenza viruses (AIVs) have been circulating in multiple avian species and are repeatedly transmitted to mammals, including humans and pigs [1,2,3]
Recent evidence suggested that H9N2 viruses isolated from China after 2010 have displayed higher virulence to chicken and mice, and some naturally isolated H9N2 viruses tested were transmissible in ferrets by respiratory droplets [4]
Phylogenetic analysis indicated that the HA genes of H9N2 viruses in China mainly fall into two lineages, the BJ/94like and G1-like [1, 3]
Summary
H9N2 avian influenza viruses (AIVs) have been circulating in multiple avian species and are repeatedly transmitted to mammals, including humans and pigs [1,2,3]. Mice are ideal animal models for investigating the pathogenic mechanisms and host range determinants of influenza virus, and they can be used to generate mouse-adapted variants by serial lung-to-lung passages [12, 13]. Some studies showed that BJ/94-like viruses could adapt well to mice [12, 14].
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