Institute of Oral Biology, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St., Pei-Tou, Taipei 11221, Taiwan.
Arch Virol. 2013 Jun;158(6):1287-96. doi: 10.1007/s00705-013-1629-3. Epub 2013 Feb 8.
Glycogen synthase kinase 3 (GSK-3) functions in the regulation of glycogen metabolism, in the cell cycle, and in immune responses and is targeted by some viruses to favor the viral life cycle. Inhibition of GSK-3 by 6-bromoindirubin-3'-acetoxime (BIO-acetoxime), a synthetic derivative of a compound from the Mediterranean mollusk Hexaplex trunculus, protects cells from varicella infection. In this study, we examined the effects of BIO-acetoxime against herpes simplex virus-1 (HSV-1) infection in human oral epithelial cells, which represent a natural target cell type. The results revealed that BIO-acetoxime relieves HSV-1-induced cytopathic effects and apoptosis. We also found that BIO-acetoxime reduced viral yields and the expression of different classes of viral proteins. Furthermore, addition of BIO-acetoxime before, simultaneously with or after HSV-1 infection significantly reduced viral yields. Collectively, BIO-acetoxime may suppress viral gene expression and protect oral epithelial cells from HSV-1 infection. These results suggest the possible involvement of GSK-3 in HSV-1 infection.
糖原合酶激酶 3（GSK-3）在糖原代谢、细胞周期和免疫反应的调节中发挥作用，一些病毒通过靶向 GSK-3 来促进病毒生命周期。6-溴靛红-3'-乙酰胺（BIO-acetoxime）是一种来自地中海软体动物Hexaplex trunculus 的化合物的合成衍生物，可抑制 GSK-3，从而保护细胞免受水痘感染。在这项研究中，我们研究了 BIO-acetoxime 对人口腔上皮细胞中单纯疱疹病毒-1（HSV-1）感染的影响，人口腔上皮细胞是一种天然的靶细胞类型。结果表明，BIO-acetoxime 缓解了 HSV-1 诱导的细胞病变效应和细胞凋亡。我们还发现 BIO-acetoxime 降低了病毒产量和不同类别的病毒蛋白的表达。此外，在 HSV-1 感染之前、同时或之后添加 BIO-acetoxime 显著降低了病毒产量。总之，BIO-acetoxime 可能抑制病毒基因表达并保护口腔上皮细胞免受 HSV-1 感染。这些结果表明 GSK-3 可能参与了 HSV-1 感染。
