| H7 subtype avian influenza virus(AIV)could mutate into a highly pathogenic avian influenza virus and cross the interspecies barrier to infect mammals,including humans.In March 2013,China reported three cases of human infection with a novel reassortant low pathogenic H7N9 subtype AIV,which was the first report in the world.So far,the H7N9 subtype AIV has caused five influenza epidemic waves in the Chinese population and poses a threat to public health.In January 2018,Jiangsu Province reported the first case of human infection with low pathogenic H7N4 subtype AIV.Therefore,it’s important to public health to perform the phylogenetic analysis of H7N4 and H7N9 subtype AIVs,and the evaluation of their infectivity and pathogenicity to mammalian hosts through mammalian experiments using ferrets and mice as models.In June 2017,an outbreak of H7N9 subtype highly pathogenic avian influenza virus of laying hens occurred at a breeding farm in Baoqing County,Shuang Yashan City,Heilongjiang Province.Six barn swallows near the farm also died abnormally during the outbreak.In this study,the organs of a dead laying hen and a dead barn swallow were collected,and two highly pathogenic H7N9 subtype AIVs were isolated.In April 2019,the spring migration time of migratory birds,we collected 1159 shorebird feces in the Yalu River Estuary Coastal Wetland National Nature Reserve in Dandong City,Liaoning Province,and isolated nine strains of H7N4 subtype low pathogenic AIV.In this study,we performed the whole genome sequence analysis of 11 H7 subtype AIVs.The results of nucleotide identity and phylogenetic analysis showed that the genomes of the two H7N9 viruses were highly homologous and closely related to the epidemic H7N9 virus in China.The genomes of nine H7N4 strains were recombined from Eurasian lineage strains,and could be divided into four genotypes according to the different origins of their internal genes;most of the gene segments of the H7N4 strains were closely related to the strains of South Korea,Japan,and Mongolia.The results of key amino acid mutations analysis showed that the M1 and NS1 proteins of 11 H7 strains exhibited mutations related to enhanced virulence to mammalian hosts.The results of the receptor-binding specificity analysis on the two H7N9 strains showed that they could both bind to the human-type(α2,6-SA)and the avian-type(α2,3-SA)receptors,but the binding avidities of the avian-type receptors are higher than the human-type receptors.The results of the ferret experiment showed that the wild bird-origin strain A/Barn Swallow/Heilongjiang/JY/2017(H7N9)was low virulent to ferrets and could not be transmitted between ferrets through droplets.The results of the mouse experiment showed that the two H7N9 and the three H7N4 representative strains could infect mice without preadaptation,and showed different pathogenicity in mice.Among them,A/eastern curlew/Liaoning/dandong1144/2019(H7N4)showed moderate pathogenicity in mice and could replicate at high levels in mouse lungs.In conclusion,the study showed that the highly pathogenic H7N9 viruses had spilled into the wild bird population;the wild bird-origin H7N4 subtype AIVs with great genetic diversity showed the characteristics of multi-subtype recombination;the wild bird-origin H7N4 and H7N9 subtype AIVs posed potential infection risks to mammals including humans.Therefore,it’s necessary to carry out long-term active monitoring of AIV carried by wild birds and to study the molecular characteristics of wild bird-origin AIV and the potential threat to mammals and humans,which can provide data and theoretical basis for early warning of avian influenza epidemics and risk assessment of public health. |
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