Transmission and pathogenicity of novel reassortants derived from Eurasian avian-like and 2009 pandemic H1N1 influenza viruses in mice and guinea pigs.

Transmission and pathogenicity of novel reassortants derived from Eurasian avian-like and 2009 pandemic H1N1 influenza viruses in mice and guinea pigs.
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源自欧亚类禽流感病毒和 2009 年大流行 H1N1 流感病毒的新型重配株在小鼠和豚鼠中的传播和致病性

DOI:
10.1038/srep27067
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发表时间:
2016-06-02
期刊:
影响因子:
4.6
通讯作者:
Liu J
Liu J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kong W;Liu Q;Sun Y;Wang Y;Gao H;Liu L;Qin Z;He Q;Sun H;Pu J;Wang D;Guo X;Yang H;Chang KC;Shu Y;Liu J

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考虑到目前欧亚类禽(EA)猪H1N1和2009年大流行(pdm/09)H1N1病毒在猪中的广泛共循环,它们之间的重配是非常合理的,但在很大程度上没有特征。在这里,用代表性EA病毒和pdm/09病毒实验性共感染猪产生了55种新的重组病毒,基于片段分离,这些病毒可被分为从Gt 1到Gt 17的17种基因型。大多数新的抑制剂是从下呼吸道分离的。在小鼠和豚鼠中,大多数弱毒株的致病性和感染性均高于亲本病毒。在豚鼠中证明的最具传播性的抗性基因型(Gt 2、Gt3、Gt 7、Gt 10和Gt 13)在小鼠中也是最致命的。值得注意的是,几乎所有这些高毒力的recritants(除Gt 13)的特点是拥有EA H1和pdm/09核糖核蛋白基因的完整的补充。在组成上,我们证明了EA H1- 222 G通过其结合禽型唾液酸受体的能力而对毒力有贡献,并且pdm/09 RNP赋予reflectants最稳健的聚合酶活性。本研究揭示了EA和pdm/09病毒在猪中的高度重配相容性,这可能产生在小鼠和豚鼠模型中具有增强的毒力和传播性的子代重配病毒。
Given the present extensive co-circulation in pigs of Eurasian avian-like (EA) swine H1N1 and 2009 pandemic (pdm/09) H1N1 viruses, reassortment between them is highly plausible but largely uncharacterized. Here, experimentally co-infected pigs with a representative EA virus and a pdm/09 virus yielded 55 novel reassortant viruses that could be categorized into 17 genotypes from Gt1 to Gt17 based on segment segregation. Majority of novel reassortants were isolated from the lower respiratory tract. Most of reassortant viruses were more pathogenic and contagious than the parental EA viruses in mice and guinea pigs. The most transmissible reassortant genotypes demonstrated in guinea pigs (Gt2, Gt3, Gt7, Gt10 and Gt13) were also the most lethal in mice. Notably, nearly all these highly virulent reassortants (all except Gt13) were characterized with possession of EA H1 and full complement of pdm/09 ribonucleoprotein genes. Compositionally, we demonstrated that EA H1-222G contributed to virulence by its ability to bind avian-type sialic acid receptors, and that pdm/09 RNP conferred the most robust polymerase activity to reassortants. The present study revealed high reassortment compatibility between EA and pdm/09 viruses in pigs, which could give rise to progeny reassortant viruses with enhanced virulence and transmissibility in mice and guinea pig models.