Transient activation of the PI3K/Akt pathway promotes Newcastle disease virus replication and enhances anti-apoptotic signaling responses.
Transient activation of the PI3K/Akt pathway promotes Newcastle disease virus replication and enhances anti-apoptotic signaling responses.
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PI3K/Akt 通路的瞬时激活促进新城疫病毒复制并增强抗凋亡信号反应
DOI：
10.18632/oncotarget.15796
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发表时间：
2017-04-04
期刊：
影响因子：
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通讯作者：
Ren T
中科院分区：
文献类型：
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作者：
Kang Y;Yuan R;Zhao X;Xiang B;Gao S;Gao P;Dai X;Feng M;Li Y;Xie P;Li Y;Gao X;Ren T
病毒感染激活宿主的细胞磷脂酰肌醇3-激酶（PI 3 K）/Akt信号通路，其参与细胞分化、生长、存活和凋亡。为了阐明纽卡斯尔病毒（NDV）致病的分子机制，我们证明了NDV在感染早期瞬时激活鸡细胞中的PI 3 K/Akt通路。感染后15 min即开始激活，24 h后逐渐减弱。在NDV感染前用PI 3 K抑制剂LY 294002或渥曼青霉素孵育细胞降低了NDV子代产量，并在感染后早期抑制Akt磷酸化。Akt激活由NDV-GM或NDV-F48 E9触发，并被甲基β-环糊精和氯丙嗪消除。NDV-La Sota感染后的治疗没有明显效果。然而，在NDV感染的早期阶段，抑制PI 3 K活化促进凋亡反应。泛半胱天冬酶抑制剂ZVAD-FMK通过抑制PI 3 K活化来减轻Akt磷酸化的减少，这表明信号传导途径促进细胞存活，进而促进病毒复制。通过抑制NDV感染后的过早凋亡，PI 3 K/Akt途径增强了抗凋亡反应。
Viral infection activates a host's cellular phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, which is involved in cell differentiation, growth, survival, and apoptosis. To elucidate molecular mechanisms in the pathogenesis of Newcastle disease virus (NDV), we demonstrated that NDV transiently activates the PI3K/Akt pathway in chicken cells at an early phase of infection. Its activation was observed as early as 15 min post-infection and gradually weakened after 24 h. Incubating cells with a PI3K inhibitor, LY294002 or wortmannin, prior to NDV infection decreased NDV progeny yields and suppressed Akt phosphorylation at early times post-infection. Akt activation is triggered by NDV-GM or NDV-F48E9 and is abolished by methyl β-cyclodextrin and chlorpromazine. Treatment following NDV-La Sota infection had no obvious effect. However, inhibiting PI3K activation promoted apoptotic responses during an early stage of NDV infection. The pan caspase inhibitor ZVAD-FMK mitigated the reduction in Akt phosphorylation by inhibiting PI3K activation, which indicates the signaling pathway promotes cell survival and, in turn, facilitates viral replication. By suppressing premature apoptosis upon NDV infection, the PI3K/Akt pathway enhances the anti-apoptotic response.