Influenza A virus NS1 protein activates the PI3K/Akt pathway to mediate antiapoptotic signaling responses
Influenza A virus NS1 protein activates the PI3K/Akt pathway to mediate antiapoptotic signaling responses
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DOI：
10.1128/jvi.02082-06
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发表时间：
2007-04-01
影响因子：
5.4
通讯作者：
Ludwig, Stephan
中科院分区：
文献类型：
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作者：
Ehrhardt, Christina;Wolff, Thorsten;Ludwig, Stephan
最近，我们已经表明，甲型流感病毒感染导致磷脂酰肌醇3-激酶（PI 3 K）/Akt通路的激活，这种细胞反应依赖于病毒非结构蛋白1（NS 1）的表达。这些数据还表明，PI 3 K活化在感染周期的中间阶段赋予病毒支持活性。到目前为止，还不知道支持病毒复制的激酶调节的过程。已经确定，在感染甲型流感病毒后，病毒NS 1的表达将β干扰素的诱导和凋亡应答保持在可耐受的限度内。在分子基础上，NS 1的这种活性被认为可以排除细胞双链RNA受体的激活以及mRNA加工的受损调节。在这里，我们提出了一种新的模式的NS 1蛋白抑制细胞凋亡诱导的行动。NS 1结合并激活PI 3 K，这导致PI 3 K效应物Akt的激活。这导致随后抑制半胱天冬酶9和糖原合酶-激酶3 β，并限制病毒诱导的细胞死亡程序。因此，NS 1不仅阻断而且激活信号通路以确保有效的病毒复制。
Recently we have shown that influenza A virus infection leads to activation of the phosphatidyllinositol 3-kinase (PI3K)/Akt pathway and that this cellular reaction is dependent on the expression of the viral nonstructural protein 1 (NS1). These data also suggested that PI3K activation confers a virus-supporting activity at intermediate stages of the infection cycle. So far it is not known which process is regulated by the kinase that supports virus replication. It is well established that upon infection with influenza A virus, the expression of the viral NS1 keeps the induction of beta interferon and the apoptotic response within a tolerable limit. On a molecular basis, this activity of NS1 has been suggested to preclude the activation of cellular double-stranded RNA receptors as well as impaired modulation of mRNA processing. Here we present a novel mode of action of the NS1 protein to suppress apoptosis induction. NS1 binds to and activates PI3K, which results in the activation of the PI3K effector Akt. This leads to a subsequent inhibition of caspase 9 and glycogen synthase-kinase 3 beta and limitation of the virus-induced cell death program. Thus, NS1 not only blocks but also activates signaling pathways to ensure efficient virus replication.