Huang Hsing-I, Chio Chi-Chong, Lin Jhao-Yin
Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
PLoS One. 2018 Jan 25;13(1):e0191617. doi: 10.1371/journal.pone.0191617. eCollection 2018.
EV71 is a positive-sense single-stranded RNA virus that belongs to the Picornaviridae family. EV71 infection may cause various symptoms ranging from hand-foot-and-mouth disease to neurological pathological conditions such as aseptic meningitis, ataxia, and acute transverse myelitis. There is currently no effective treatment or vaccine available. Various compounds have been examined for their ability to restrict EV71 replication. However, most experiments have been performed in rhabdomyosarcoma or Vero cells. Since the gastrointestinal tract is the entry site for this pathogen, we anticipated that orally ingested agents may exert beneficial effects by decreasing virus replication in intestinal epithelial cells. In this study, curcumin (diferuloylmethane, C21H20O6), an active ingredient of turmeric (Curcuma longa Linn) with anti-cancer properties, was investigated for its anti-enterovirus activity. We demonstrate that curcumin treatment inhibits viral translation and increases host cell viability. Curcumin does not exert its anti-EV71 effects by modulating virus attachment or virus internal ribosome entry site (IRES) activity. Furthermore, curcumin-mediated regulation of mitogen-activated protein kinase (MAPK) signaling pathways is not involved. We found that protein kinase C delta (PKCδ) plays a role in virus translation in EV71-infected intestinal epithelial cells and that curcumin treatment decreases the phosphorylation of this enzyme. In addition, we show evidence that curcumin also limits viral translation in differentiated human intestinal epithelial cells. In summary, our data demonstrate the anti-EV71 properties of curcumin, suggesting that ingestion of this phytochemical may protect against enteroviral infections.
肠道病毒71型(EV71)是一种正链单链RNA病毒,属于小RNA病毒科。EV71感染可能导致从手足口病到无菌性脑膜炎、共济失调和急性横贯性脊髓炎等神经病理状况的各种症状。目前尚无有效的治疗方法或疫苗。人们已经对各种化合物限制EV71复制的能力进行了研究。然而,大多数实验是在横纹肌肉瘤或非洲绿猴肾(Vero)细胞中进行的。由于胃肠道是这种病原体的进入部位,我们预计口服药物可能通过减少肠道上皮细胞中的病毒复制而发挥有益作用。在本研究中,我们研究了姜黄素(二阿魏酰甲烷,C21H20O6),一种具有抗癌特性的姜黄(Curcuma longa Linn)活性成分的抗肠道病毒活性。我们证明姜黄素处理可抑制病毒翻译并提高宿主细胞活力。姜黄素并非通过调节病毒附着或病毒内部核糖体进入位点(IRES)活性来发挥其抗EV71作用。此外,姜黄素介导的丝裂原活化蛋白激酶(MAPK)信号通路的调节也未涉及。我们发现蛋白激酶Cδ(PKCδ)在EV71感染的肠道上皮细胞的病毒翻译中起作用,并且姜黄素处理可降低该酶的磷酸化。此外,我们还证明姜黄素也限制分化的人肠道上皮细胞中的病毒翻译。总之,我们的数据证明了姜黄素的抗EV71特性,表明摄入这种植物化学物质可能预防肠道病毒感染。