Mouse-adapted H9N2 avian influenza virus causes systemic infection in mice

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.

Increased Pulmonary Pneumococcal Clearance after Resolution of H9N2 Avian Influenza Virus Infection in Mice

“…The virus had been completely eliminated from the lungs of H9N2-infected mice by 14 dpi, and lung histopathology in H9N2-infected mice was similar to that in mock-infected mice at 14 dpi. These results showed that H9N2 virus infection caused obvious respiratory diseases in BALB/c mice and mice infected with H9N2 virus had recovered by 14 dpi, which was consistent with our previous and other published research findings ( 38 – 40 ).…”

“…The virus had been completely eliminated from the lungs of H9N2-infected mice by 14 D.P.I., and lung histopathology in H9N2-infected mice was similar to that in mock-infected mice on 14 D.P.I. These results showed that H9N2 virus infection caused obvious respiratory diseases in BALB/c mice and mice infected with H9N2 virus had recovered by 14 D.P.I., which were consistent with our previous and other published research findings(38)(39)(40).Although influenza virus alone could cause a substantial impact on global health, secondary bacterial infections post-influenza are associated with increased morbidity and mortality during both epidemic and pandemic influenza(23). Secondary bacterial on March 21, 2021 by guest http://iai.asm.org/ Downloaded from pneumonia, particularly from S. pneumoniae, accounts for more than 95% and 50% of severe illnesses and deaths that occurred during 1918 pandemic and 2009 pandemic, respectively(17-20).…”

Real-Time Visualization of the Infection and Replication of a Mouse-Lethal Recombinant H9N2 Avian Influenza Virus

“…In general, H9N2 infections in poultry or human are mild. However, some H9N2 AIVs were reported to cause lethal infection in mice (20)(21)(22). To better understand the mechanisms, we generated a mouse-lethal recombinant H9N2 AIV (V K627 -NanoLuc virus) to analyze the real-time infection dynamic of H9N2 AIV in mice.…”

“…Previous studies have shown that the H9N2 AIVs generally caused mild infections in poultry, even in humans. Notably, some H9N2 AIVs were found to replicate efficiently and possess lethality in mice (20)(21)(22), but the viral infection dynamics in vivo and the detailed mechanisms of increased pathogenicity of H9N2 AIVs to mice remain unclear, posing a potential threat to public health.…”

Animal Models Utilized for the Development of Influenza Virus Vaccines

“…This process involves infecting mice with the wild type strain, collecting mouse lungs at one to three days post infection, homogenizing lung tissues and then infecting another mouse with diluted lung homogenates. Some viruses are easily adapted to mice, however other viruses may take several passages before they are fully adapted [ 122 , 123 , 124 , 125 ]. Mouse adaptation can cause mutations in many viral genes, including the polymerase machinery (PB1, PB2 and PA) as well as the glycoproteins HA and NA [ 126 , 127 , 128 ].…”