The role of the PI3K-Akt signal transduction pathway in Autographa californica multiple nucleopolyhedrovirus infection of Spodoptera frugiperda cells.
The role of the PI3K-Akt signal transduction pathway in Autographa californica multiple nucleopolyhedrovirus infection of Spodoptera frugiperda cells.
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DOI：
10.1016/j.virol.2009.06.007
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发表时间：
2009-08
期刊：
影响因子：
3.7
通讯作者：
W. Xiao;Yi Yang;Qingbei Weng;Tiehao Lin;M. Yuan;Kai Yang;Y. Pang
中科院分区：
文献类型：
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作者：
W. Xiao;Yi Yang;Qingbei Weng;Tiehao Lin;M. Yuan;Kai Yang;Y. Pang
杆状病毒科是一种感染节肢动物的多种病原体。这些病毒已在全世界600多种寄主物种中被发现，主要来自鳞翅目昆虫，但也来自双翅目和膜翅目昆虫（Rohrmann， 2008年）。杆状病毒在被脂质包膜包裹的杆状衣壳内含有一个大的、圆形的双链DNA基因组（范围从80到180kbp） （Theilmann et al., 2005）。杆状病毒科的原型病毒加州自签名多核多角体病毒（AcMNPV）在感染周期内产生两种病毒粒子。这导致病毒在受感染的昆虫幼虫内有效复制，并在自然界中进行昆虫对昆虫的病毒传播。闭塞源病毒位于闭塞体（OBs）内，通过口腔感染在昆虫之间传播。出芽病毒（BVs）由受感染的中肠上皮细胞产生，可引发继发性感染（Federici, 1997）。最近的研究表明，许多病毒能够调节细胞事件，特别是那些控制细胞凋亡和细胞存活的事件，从而允许有效的复制和后代生产（Ji和Liu, 2008; Cooray, 2007）。磷脂酰肌醇3-激酶(PI3K)-Akt信号通路在细胞存活、凋亡、增殖、迁移、分化和代谢调节中发挥重要作用。近年来，越来越多的研究表明，许多病毒可以激活PI3K-Akt信号通路。例如，在人肺癌细胞甲型流感/PR/8/34感染的晚期，Akt（也称为蛋白激酶B）磷酸化水平升高，PI3K抑制剂LY294002抑制PI3K-Akt的激活，导致病毒RNA合成、病毒蛋白表达和病毒产量降低（Shin等，2007）。PI3K由一个调控亚基（p85）和一个催化亚基（p110）组成，具有蛋白激酶和脂质激酶活性（Nurnberg, 2003; Dhand et al., 1994）。对哺乳动物细胞的研究表明，PI3K可被许多不同的有丝分裂信号（如表皮生长因子）激活（Stoyanov等，1995）。活化的PI3K优先磷酸化膜磷脂磷脂肌醇(4,5)-二磷酸，生成磷脂肌醇(3,4,5)-三磷酸。磷脂酰肌醇(3,4,5)-三磷酸作为招募pleckstrin同源结构域蛋白的第二信使，如Akt和磷酸肌醇依赖性激酶1。Akt是一种细胞质丝氨酸/苏氨酸激酶，也是PI3K的主要效应因子。Akt的激活是由丝氨酸473 （Ser 473）和苏氨酸308 （Thr 308）残基磷酸化介导的，通过pi3k依赖或不依赖的机制（Meier等人，1997；Welch等人，1998）。磷酸化的Akt在调节多种下游信号中起核心作用
Baculoviridae is a diverse family of pathogens that infects arthropods. These viruses have been detected worldwide in over 600 host species, predominantly from insects of the order Lepidoptera but also from the orders Diptera and Hymenoptera (Rohrmann, 2008). Baculoviruses contain a large, circular, double-stranded DNA genome (ranging from 80 to 180 kbp) within a rod-shaped capsid that is enclosed within a lipid envelope (Theilmann et al., 2005). The prototype virus of Baculoviridae, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), produce two types of virions during the infection cycle. This results in efficient viral replication within infected insect larvae and insect-to-insect viral spread in nature. Occlusion-derived viruses, located within occlusion bodies (OBs), are transmitted from insect to insect via oral infection. Budded viruses (BVs) are produced from infected midgut epithelial cells and can initiate a secondary infection (Federici, 1997). Recent work has shown that many viruses are able to modulate cellular events, particularly those governing apoptosis and cellular survival, thereby allowing efficient replication and progeny production (Ji and Liu, 2008; Cooray, 2007). The phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway plays an important role in cell survival, apoptosis, proliferation, migration, differentiation, and metabolic regulation. Recently, an increasing number of studies have demonstrated that many viruses can activate the PI3K-Akt signaling pathway. For example, Akt (also known as protein kinase B) phosphorylation is elevated in the late phase of influenza A/PR/8/34 infection in human lung carcinoma cells, and inhibition of PI3K-Akt activation by LY294002, a PI3K inhibitor, results in reduced viral RNA synthesis, viral protein expression, and viral yield (Shin et al., 2007). PI3K consists of a regulatory subunit (p85) and a catalytic subunit (p110) and exhibits both protein kinase and lipid kinase activities (Nurnberg, 2003; Dhand et al., 1994). Studies in mammalian cells have demonstrated that PI3K is activated by many different mitogenic signals (eg, epidermal growth factor)(Stoyanov et al., 1995). Activated PI3K preferentially phosphorylates the membrane phospholipid, phosphatidylinositol (4, 5)-biphosphate, to produce phosphatidylinositol (3, 4, 5)-triphosphate. Phosphatidylinositol (3, 4, 5)-triphosphate functions as a second messenger to recruit pleckstrin homology domain-containing proteins, such as Akt and phosphoinositide-dependent kinase 1. Akt is a cytoplasmic serine/threonine kinase and a major PI3K effector. Activation of Akt is mediated by phosphorylation of both serine 473 (Ser 473) and threonine 308 (Thr 308) residues through either a PI3K-dependent or-independent mechanism (Meier et al., 1997; Welch et al., 1998). Phosphorylated Akt plays a central role in modulating diverse downstream signaling