A dual character of flavonoids in influenza A virus replication and spread through modulating cell-autonomous immunity by MAPK signaling pathways.
A dual character of flavonoids in influenza A virus replication and spread through modulating cell-autonomous immunity by MAPK signaling pathways.
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DOI：
10.1038/srep07237
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发表时间：
2014-11-28
影响因子：
4.6
通讯作者：
Liang W
中科院分区：
文献类型：
--
作者：
Dong W;Wei X;Zhang F;Hao J;Huang F;Zhang C;Liang W
黄酮类化合物是一类多酚类化合物，具有多种生理活性，包括抗流感病毒活性。利用流感病毒A/WSN/33感染的A549细胞，从天然黄酮类化合物库中筛选抗流感病毒药物。出乎意料的是，一些类黄酮化合物显着抑制病毒复制，而其他显着促进病毒复制。在这项研究中，我们试图了解黄酮类化合物在抗病毒机制方面的这些差异。橙皮苷和山奈酚被选为双方的代表，它们对流感病毒复制的作用相反。我们的研究表明，橙皮苷和山奈酚对流感病毒产生相反的作用是由于选择性地调节MAP激酶通路，诱导相反的细胞自主免疫反应：橙皮苷上调P38和JNK的表达和激活，从而增强细胞自主免疫;而山奈酚显著下调p38和JNK的表达和激活，从而抑制细胞自主免疫。此外，橙皮苷通过下调ERK的激活限制RNP从细胞核的输出，而山奈酚通过上调ERK的激活促进RNP的输出。我们的研究结果表明，新一代的抗流感病毒药物可以开发的基础上选择性调节MAP激酶途径，刺激细胞自主免疫。
Flavonoids are well known as a large class of polyphenolic compounds, which have a variety of physiological activities, including anti-influenza virus activity. The influenza A/WSN/33 infected A549 cells have been used to screen anti-influenza virus drugs from natural flavonoid compounds library. Unexpectedly, some flavonoid compounds significantly inhibited virus replication, while the others dramatically promoted virus replication. In this study, we attempted to understand these differences between flavonoid compounds in their antivirus mechanisms. Hesperidin and kaempferol were chosen as representatives of both sides, each of which exhibited the opposite effects on influenza virus replication. Our investigation revealed that the opposite effects produced by hesperidin and kaempferol on influenza virus were due to inducing the opposite cell-autonomous immune responses by selectively modulating MAP kinase pathways: hesperidin up-regulated P38 and JNK expression and activation, thus resulting in the enhanced cell-autonomous immunity; while kaempferol dramatically down-regulated p38 and JNK expression and activation, thereby suppressing cell-autonomous immunity. In addition, hesperidin restricted RNPs export from nucleus by down-regulating ERK activation, but kaempferol promoted RNPs export by up-regulating ERK activation. Our findings demonstrate that a new generation of anti-influenza virus drugs could be developed based on selective modulation of MAP kinase pathways to stimulate cell-autonomous immunity.
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影响因子：
11.4
作者：
Goh, KC;Haque, SJ;Williams, BRG
通讯作者：
Williams, BRG
影响因子：
168.9
作者：
Gubareva, LV;Kaiser, L;Hayden, FG
通讯作者：
Hayden, FG
影响因子：
3.7
作者：
Lee SM;Gardy JL;Cheung CY;Cheung TK;Hui KP;Ip NY;Guan Y;Hancock RE;Peiris JS
通讯作者：
Peiris JS
DOI：
10.1016/j.biocel.2007.06.013
发表时间：
2007-01-01
影响因子：
4
作者：
Humar, Matjaz;Loop, Torsten;Pannen, Benedikt H. J.
通讯作者：
Pannen, Benedikt H. J.
影响因子：
6.4
作者：
Hui, Kenrie P. Y.;Lee, Suki M. Y.;Peiris, J. S. M.
通讯作者：
Peiris, J. S. M.