Abstract：
AMP-activated protein kinase (AMPK) is a cellular energy sensor regulating metabolic homeostasis. In this study, we investigated the role of AMPK in response to human herpesvirus 6A (HHV-6A) infection. We show that HHV-6A infection significantly downregulates the active phosphorylated state of AMPK in infected T cells. Pharmacological activation of AMPK highly attenuated HHV-6A propagation. Mechanistically, we found that the activation of AMPK by AICAR blocked HHV-6-induced glycolysis by inhibiting glucose metabolism and lactate secretion, as well as decreasing expressions of key glucose transporters and glycolytic enzymes. In addition, mTOR signaling has been inactivated in HHV-6A infected T cells by AICAR treatment. We also showed that HHV-6A infection of human umbilical cord blood mononuclear cells (CBMCs) reduced AMPK activity whereas the activation of AMPK by metformin drastically reduced HHV-6A DNA replication and virions production. Taken together, this study demonstrates that AMPK is a promising antiviral therapeutic target against HHV-6A infection.
摘要：
AMP激活的蛋白激酶（AMPK）是一种调节代谢稳态的细胞能量传感器。在这项研究中,我们研究了AMPK在人类疱疹病毒6A(HHV-6A)感染应答中的作用.我们显示HHV-6A感染显著下调感染T细胞中AMPK的活性磷酸化状态。AMPK的药理学激活高度减弱HHV-6A传播。机械上,我们发现AICAR激活AMPK通过抑制葡萄糖代谢和乳酸分泌阻断HHV-6诱导的糖酵解,以及降低关键葡萄糖转运蛋白和糖酵解酶的表达。此外,通过AICAR处理,mTOR信号在HHV-6A感染的T细胞中被灭活。我们还表明，人脐带血单核细胞（CBMC）的HHV-6A感染降低了AMPK活性，而二甲双胍对AMPK的激活大大降低了HHV-6ADNA复制和病毒体的产生。一起来看,这项研究表明，AMPK是针对HHV-6A感染的一个有前途的抗病毒治疗靶点。
