Internal Gene Cassette from a Genotype S H9N2 Avian Influenza Virus Attenuates the Pathogenicity of H5 Viruses in Chickens and Mice.

Internal Gene Cassette from a Genotype S H9N2 Avian Influenza Virus Attenuates the Pathogenicity of H5 Viruses in Chickens and Mice.
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基因型 S H9N2 禽流感病毒的内部基因盒可减弱 H5 病毒对鸡和小鼠的致病性

DOI:
10.3389/fmicb.2017.01978
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发表时间:
2017
影响因子:
5.2
通讯作者:
Liu X
Liu X
中科院分区:
生物学2区
文献类型:
--
作者:
Hao X;Wang J;Hu J;Lu X;Gao Z;Liu D;Li J;Wang X;Gu M;Hu Z;Liu X;Hu S;Xu X;Peng D;Jiao X;Liu X

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S基因型H9N2禽流感病毒(AIV)经常捐献内部基因,以促进H7N9、H10N8、H5N2和H5N6 AIV等新型重配病毒的产生,对人类健康和家禽业构成巨大威胁。然而,内部基因盒为 S H9N2 的重配 H5 病毒在鸡和小鼠中的致病性和传播仍不清楚。在这项研究中,通过反向遗传学产生了四个 H5 重配体,它们携带来自 H5 病毒不同分支的 HA 和 NA 基因,以及来自主要基因型 S 的 H9N2 病毒的其余内部基因。我们发现所有四种 H5 重配病毒在鸡和小鼠中均表现出毒力减弱,因此与相应的亲本病毒相比,导致平均死亡时间增加。一致的是,与各自的亲本病毒相比,哺乳动物和鸟类细胞中的聚合酶活性和复制能力以及鸡和小鼠肺部的细胞因子反应也有所降低。此外,这些重配体通过直接接触在鸟类之间传播,而不是通过空气传播。我们的数据表明,来自基因型 S H9N2 病毒的内部基因作为一个完整盒,在降低 H5 重组体对鸡和小鼠的致病性方面发挥着重要作用,并可能有助于鸟类或哺乳动物宿主的循环。
H9N2 avian influenza virus (AIV) of genotype S frequently donate internal genes to facilitate the generation of novel reassortants such as H7N9, H10N8, H5N2 and H5N6 AIVs, posing an enormous threat to both human health and poultry industry. However, the pathogenicity and transmission of reassortant H5 viruses with internal gene cassette of genotype S H9N2-origin in chickens and mice remain unknown. In this study, four H5 reassortants carrying the HA and NA genes from different clades of H5 viruses and the remaining internal genes from an H9N2 virus of the predominant genotype S were generated by reverse genetics. We found that all four H5 reassortant viruses showed attenuated virulence in both chickens and mice, thus leading to increased the mean death times compared to the corresponding parental viruses. Consistently, the polymerase activity and replication ability in mammalian and avian cells, and the cytokine responses in the lungs of chickens and mice were also decreased when compared to their respective parental viruses. Moreover, these reassortants transmitted from birds to birds by direct contact but not by an airborne route. Our data indicate that the internal genes as a whole cassette from genotype S H9N2 viruses play important roles in reducing the pathogenicity of the H5 recombinants in chickens and mice, and might contribute to the circulation in avian or mammalian hosts.
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