Institute of Oral Biology, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St., Pei-Tou, Taipei 11221, Taiwan.
Virus Res. 2010 Oct;153(1):36-43. doi: 10.1016/j.virusres.2010.07.002. Epub 2010 Jul 8.
Phosphatidylinositol 3-kinases (PI3Ks) function in the anti-apoptotic pathway, and are commonly exploited by various viruses to accomplish the viral life cycle. This study examined the role of the PI3K pathway in human oral epithelial cells following herpes simplex virus type 1 (HSV-1) infection. The results showed that HSV-1 induced the phosphorylation of Akt and glycogen synthase kinase 3 (GSK-3). Phosphorylation of Akt, but not GSK-3, induced by HSV-1 was PI3K-dependent. The expression of HSV-1 immediate-early genes may be involved in the initial phosphorylation of Akt and GSK-3. Inhibition of HSV-1-induced PI3K activity increased DNA fragmentation and cleavage of poly ADP-ribose polymerase (PARP), caspase 3 and caspase 7 compared with infected alone. Inhibition of PI3K attenuated the expression of HSV-1-infected cell protein 0 (ICP0), but not thymidine kinase (TK) and viral replication. Collectively, these data suggested that, in oral epithelial cells, the HSV-1-induced PI3K/Akt activation was involved in the regulation of apoptosis blockage and viral gene expression.
磷脂酰肌醇 3-激酶（PI3Ks）在抗细胞凋亡途径中发挥作用，并且通常被各种病毒利用来完成病毒生命周期。本研究探讨了单纯疱疹病毒 1（HSV-1）感染人口腔上皮细胞后 PI3K 途径的作用。结果表明，HSV-1 诱导 Akt 和糖原合成酶激酶 3（GSK-3）的磷酸化。HSV-1 诱导的 Akt 磷酸化而不是 GSK-3 磷酸化是 PI3K 依赖性的。HSV-1 早期基因的表达可能参与 Akt 和 GSK-3 的初始磷酸化。与单独感染相比，抑制 HSV-1 诱导的 PI3K 活性增加了 DNA 片段化和聚 ADP-核糖聚合酶（PARP）、半胱天冬酶 3 和半胱天冬酶 7 的切割。抑制 PI3K 减弱了 HSV-1 感染细胞蛋白 0（ICP0）的表达，但不减弱胸苷激酶（TK）和病毒复制。总之，这些数据表明，在口腔上皮细胞中，HSV-1 诱导的 PI3K/Akt 激活参与了凋亡阻断和病毒基因表达的调节。
