The Mobility of Eurasian Avian-like M2 Is Determined by Residue E79 Which Is Essential for Pathogenicity of 2009 Pandemic H1N1 Influenza Virus in Mice.
The Mobility of Eurasian Avian-like M2 Is Determined by Residue E79 Which Is Essential for Pathogenicity of 2009 Pandemic H1N1 Influenza Virus in Mice.
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DOI：
10.3390/v15122365
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发表时间：
2023-11-30
期刊：
影响因子：
--
通讯作者：
Ma J
中科院分区：
文献类型：
--
作者：
Wu R;Zeng X;Wu M;Xie L;Xu G;Mao Y;Wang Z;Cheng Y;Wang H;Yan Y;Sun J;Ma J
2009年，一种新型H1N1流感病毒引起了21世纪世纪的第一次流感大流行。研究表明，流感病毒M基因在2009年H1N1大流行（（H1N1）pdm 09）的致病性和传播性中发挥了重要作用，但其潜在机制尚不清楚。流感病毒M基因编码两种蛋白质，基质蛋白1和基质蛋白2，其在病毒复制和组装中起重要作用。在这项研究中，发现（H1N1）pdm 09病毒的M2蛋白在聚丙烯酰胺凝胶电泳（PAGE）中显示出比北美三重耐药流感M2蛋白更低的迁移率。（H1N1）pdm 09 M2的氨基酸的定点突变揭示了E79负责迁移率变化。进一步的动物研究表明，与小鼠中的野生型病毒相比，含有单个M2-E79 K的（H1N1）pdm 09显著减毒，并且在小鼠肺中诱导较低的促炎细胞因子和IFN。进一步的体外研究表明，该突变也影响NLRP 3炎性小体激活。为了揭示它们具有不同迁移率的原因，采用圆二色性光谱分析，并显示两种M2蛋白显示不同的二级结构。总之，我们的研究结果表明，M2 E79是重要的病毒复制和致病性（H1N1）pdm 09通过NLRP 3炎性小体和促炎反应。
In 2009, a novel H1N1 influenza virus caused the first influenza pandemic of the 21st century. Studies have shown that the influenza M gene played important roles in the pathogenicity and transmissibility of the 2009 H1N1 pandemic ((H1N1)pdm09), whilst the underlying mechanism remains unclear. The influenza M gene encodes two proteins, matrix protein 1 and matrix protein 2, which play important roles in viral replication and assembly. In this study, it is found that the M2 protein of the (H1N1)pdm09 virus showed a lower mobility rate than the North America triple-reassortant influenza M2 protein in Polyacrylamide Gel Electrophoresis (PAGE). The site-directed mutations of the amino acids of (H1N1)pdm09 M2 revealed that E79 is responsible for the mobility rate change. Further animal studies showed that the (H1N1)pdm09 containing a single M2-E79K was significantly attenuated compared with the wild-type virus in mice and induced lower proinflammatory cytokines and IFNs in mouse lungs. Further in vitro studies indicated that this mutation also affected NLRP3 inflammasome activation. To reveal the reason why they have different mobility rates, a circular dichroism spectra assay was employed and showed that the two M2 proteins displayed different secondary structures. Overall, our findings suggest that M2 E79 is important for the virus replication and pathogenicity of (H1N1)pdm09 through NLRP3 inflammasome and proinflammatory response.
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影响因子：
3.7
作者：
Rossman JS;Lamb RA
通讯作者：
Lamb RA
DOI：
10.3390/v10090461
发表时间：
2018-08-28
期刊：
Viruses
影响因子：
--
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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