The PB2 and M genes are critical for the superiority of genotype S H9N2 virus to genotype H in optimizing viral fitness of H5Nx and H7N9 avian influenza viruses in mice
The PB2 and M genes are critical for the superiority of genotype S H9N2 virus to genotype H in optimizing viral fitness of H5Nx and H7N9 avian influenza viruses in mice
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PB2和M基因对于S基因型H9N2病毒在优化H5Nx和H7N9禽流感病毒在小鼠体内的病毒适应性方面优于H基因型至关重要
DOI：
10.1111/tbed.13395
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发表时间：
2019-11-08
影响因子：
4.3
通讯作者：
Liu, Xiufan
中科院分区：
文献类型：
--
作者：
Hao, Xiaoli;Hu, Jiao;Liu, Xiufan
自2010年以来，基因型S H9 N2禽流感病毒在中国占主导地位，其整个内部基因盒贡献了新型流感病毒的产生，包括H5 Nx，H7N9和H10 N8病毒，这些病毒对家禽和人类构成巨大威胁。基因型S H9 N2病毒的一个关键特征是G1样M和PB 2基因取代了基因型H病毒早期的F/98样M和PB 2基因。然而，这种基因替换如何影响哺乳动物中新出现的流感病毒的病毒适应性仍不清楚。我们在这里报告，在细胞培养物以及小鼠模型中，具有基因型S内部基因盒的H5 Nx和H7N9病毒显示出比具有基因型H内部基因盒的病毒增强的复制和毒力。我们发现，G1-like PB 2基因与增加的聚合酶活性和改善核积累相比，F/98-like对应，而G1-like M基因促进RNP有效易位到细胞质。我们的研究结果表明，基因型S H9 N2内部基因盒，其中具有G1样M和PB 2基因，是上级基因型H，在优化病毒的健身，从而有影响评估这些基因的引入，以产生新的流感病毒的潜在风险。
Genotype S H9N2 avian influenza virus, which has been predominant in China since 2010, contributed its entire internal gene cassette to the genesis of novel reassortant influenza viruses, including H5Nx, H7N9 and H10N8 viruses that pose great threat to poultry and humans. A key feature of the genotype S H9N2 virus is the substitution of G1-like M and PB2 genes for the earlier F/98-like M and PB2 of genotype H virus. However, how this gene substitution has influenced viral adaptability of emerging influenza viruses in mammals remains unclear. We report here that reassortant H5Nx and H7N9 viruses with the genotype S internal gene cassette displayed enhanced replication and virulence over those with genotype H internal gene cassette in cell cultures as well as in the mouse models. We showed that the G1-like PB2 gene was associated with increased polymerase activity and improved nuclear accumulation compared with the F/98-like counterpart, while the G1-like M gene facilitated effective translocation of RNP to cytoplasm. Our findings suggest that the genotype S H9N2 internal gene cassette, which possesses G1-like M and PB2 genes, is superior to that of genotype H, in optimizing viral fitness, and thus have implications for assessing the potential risk of these gene introductions to generate emerging influenza viruses.