Meier Jeffery L, Grose Charles
Virology laboratories, Department of Internal Medicine, University of Iowa, Iowa City, IA.
Department of Pediatrics, University of Iowa, Iowa City, IA.
Yale J Biol Med. 2017 Mar 29;90(1):25-33. eCollection 2017 Mar.
Trehalose is a non-reducing sugar formed from two glucose units. Trehalose induces abundant autophagy in cultured cells and also reduces the rate of aggregation of the huntingtin protein in the animal model of Huntington disease, a chronic neurological disease in humans. The mechanism of this effect on autophagy is now known to be caused by starvation secondary to inhibition of a family of glucose transporters known as the solute carrier 2 or the glucose transporter family. Variable effects of trehalose treatment have been observed during infections with two herpesviruses-human cytomegalovirus and varicella-zoster virus. The reasons for differing results have now been delineated. These differences are caused by two variables in conditions of infection: timing of addition of trehalose and type of inoculum (cell-free virus vs. infected cells). When monolayers pretreated with trehalose were inoculated with cell-free virus, there was a decline in virus spread by as much as 93 percent when compared with untreated monolayers. However, when monolayers were inoculated with infected cells rather than cell-free virus, there was no decline in virus spread. These results demonstrated that the effect of trehalose was limited to monolayers that were starved when inoculated with cell-free virus. In contrast, sufficient virus was already present in infected cell inocula so as to minimize any inhibitory effect of a starved monolayer. These results also showed that trehalose did not specifically inhibit a herpesvirus; rather, addition of trehalose to cell culture media altered the intracellular environment.
海藻糖是一种由两个葡萄糖单位组成的非还原性糖。海藻糖可在培养细胞中诱导大量自噬，还能降低亨廷顿舞蹈病动物模型中亨廷顿蛋白的聚集速率，亨廷顿舞蹈病是人类的一种慢性神经疾病。现在已知这种对自噬的作用机制是由抑制一类称为溶质载体2或葡萄糖转运蛋白家族的葡萄糖转运体继发的饥饿引起的。在感染两种疱疹病毒——人类巨细胞病毒和水痘带状疱疹病毒期间，观察到了海藻糖治疗的不同效果。现在已经明确了结果不同的原因。这些差异是由感染条件中的两个变量引起的：海藻糖添加的时间和接种物的类型（无细胞病毒与感染细胞）。当用无细胞病毒接种经海藻糖预处理的单层细胞时，与未处理的单层细胞相比，病毒传播下降了多达93%。然而，当用感染细胞而不是无细胞病毒接种单层细胞时，病毒传播没有下降。这些结果表明，海藻糖的作用仅限于接种无细胞病毒时处于饥饿状态的单层细胞。相比之下，感染细胞接种物中已经存在足够的病毒，从而使饥饿单层细胞的任何抑制作用最小化。这些结果还表明，海藻糖并没有特异性抑制疱疹病毒；相反，向细胞培养基中添加海藻糖改变了细胞内环境。
