Inability of NS1 protein from an H5N1 influenza virus to activate PI3K/Akt signaling pathway correlates to the enhanced virus replication upon PI3K inhibition.
Inability of NS1 protein from an H5N1 influenza virus to activate PI3K/Akt signaling pathway correlates to the enhanced virus replication upon PI3K inhibition.
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H5N1 流感病毒的 NS1 蛋白无法激活 PI3K/Akt 信号通路与 PI3K 抑制后病毒复制增强相关
DOI：
10.1186/1297-9716-43-36
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发表时间：
2012-04-24
影响因子：
4.4
通讯作者：
Li K
中科院分区：
文献类型：
--
作者：
Li W;Wang G;Zhang H;Shen Y;Dai J;Wu L;Zhou J;Jiang Z;Li K
磷脂酰肌醇3-激酶(PI3K)/Akt信号通路在甲型流感病毒感染过程中被激活，可通过多种机制促进病毒复制。Ns1蛋白与PI3K的P85β亚基直接结合是激活PI3K/Akt信号通路所必需的。PI3K的结合和随后的激活被认为是甲型流感病毒NS1蛋白的保守特征。不同甲型流感病毒中NS1蛋白的序列变异使我们研究了可能偏离保守性的情况。本研究检测了四种甲型流感病毒不同亚型/毒株的Ns1蛋白与PI3K的P85β亚基结合和激活PI3K/Akt的能力。除H5N1病毒(A/鸡/广东/1/05，简记为GD05)的NS1蛋白与P85β结合但不能激活PI3K/Akt外，其余蛋白均能与P85β结合并激活PI3K/Akt，提示NS1中的未知结构域(S)可能参与了PI3K的激活。此外，PI3K抑制剂LY294002不能抑制GD05病毒的复制，但能显著增加病毒的复制。我们的研究表明，NS1蛋白激活PI3K/Akt在甲型流感病毒中并不是高度保守的，抑制PI3K/Akt通路作为一种抗流感策略可能并不适用于所有甲型流感病毒。
Phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, activated during influenza A virus infection, can promote viral replication via multiple mechanisms. Direct binding of NS1 protein to p85β subunit of PI3K is required for activation of PI3K/Akt signaling. Binding and subsequent activation of PI3K is believed to be a conserved character of influenza A virus NS1 protein. Sequence variation of NS1 proteins in different influenza A viruses led us to investigate possible deviation from the conservativeness. In the present study, NS1 proteins from four different influenza A virus subtypes/strains were tested for their ability to bind p85β subunit of PI3K and to activate PI3K/Akt. All NS1 proteins efficiently bound to p85β and activated PI3K/Akt, with the exception of NS1 protein from an H5N1 virus (A/Chicken/Guangdong/1/05, abbreviated as GD05), which bound to p85β but failed to activate PI3K/Akt, implying that as-yet-unidentified domain(s) in NS1 may alternatively mediate the activation of PI3K. Moreover, PI3K inhibitor, LY294002, did not suppress but significantly increased the replication of GD05 virus. Our study indicates that activation of PI3K/Akt by NS1 protein is not highly conserved among influenza A viruses and inhibition of the PI3K/Akt pathway as an anti-influenza strategy may not work for all influenza A viruses.
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影响因子：
16
作者：
Nemeroff, ME;Barabino, SML;Krug, RM
通讯作者：
Krug, RM
DOI：
10.1073/pnas.0710907105
发表时间：
2008-03-25
影响因子：
11.1
作者：
Kaur, Surinder;Sassano, Antonella;Platanias, Leonidas C.
通讯作者：
Platanias, Leonidas C.
影响因子：
5.4
作者：
Mannová, P;Beretta, L
通讯作者：
Beretta, L
影响因子：
56.9
作者：
Miled, Nabil;Yan, Ying;Williams, Roger L.
通讯作者：
Williams, Roger L.
影响因子：
4.8
作者：
Li, Yang;Anderson, Deborah H.;Zhou, Yan
通讯作者：
Zhou, Yan