Department of Cancer Biology, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):1951-6. doi: 10.1073/pnas.1310779111. Epub 2014 Jan 21.
Carbohydrate-response element binding protein (ChREBP) plays a key role in regulating glucose metabolism and de novo lipogenesis in metabolic tissues and cancer cells. Here we report that ChREBP is also a critical regulator of the metabolic alterations induced during human cytomegalovirus (HCMV) infection. The expression of both ChREBP-α and ChREBP-β is robustly induced in HCMV-infected human fibroblasts; this induction is required for efficient HCMV infection. Depletion of ChREBP in HCMV-infected cells results in reduction of HCMV-induced glucose transporter 4 and glucose transporter 2 expression, leading to inhibition of glucose uptake, lactate production, nucleotide biosynthesis, and NADPH generation. We previously reported that HCMV infection induces lipogenesis through the activation of sterol regulatory element binding protein 1, which is mediated by the induction of PKR-like endoplasmic reticulum kinase. Data from the present study show that HCMV-induced lipogenesis is also controlled by the induction of ChREBP, in a second mechanism involved in the regulation of HCMV-induced de novo lipogenesis. These results suggest that ChREBP plays a key role in reprogramming glucose and lipid metabolism in HCMV infection.
碳水化合物反应元件结合蛋白（ChREBP）在调节代谢组织和癌细胞中的葡萄糖代谢和从头脂肪生成中发挥关键作用。在这里，我们报告 ChREBP 也是人巨细胞病毒（HCMV）感染期间诱导代谢改变的关键调节剂。在 HCMV 感染的人成纤维细胞中，ChREBP-α 和 ChREBP-β 的表达均被强烈诱导；这种诱导对于有效的 HCMV 感染是必需的。在 HCMV 感染的细胞中耗尽 ChREBP 会导致 HCMV 诱导的葡萄糖转运蛋白 4 和葡萄糖转运蛋白 2 表达减少，从而抑制葡萄糖摄取、乳酸生成、核苷酸生物合成和 NADPH 生成。我们之前报道过，HCMV 感染通过激活固醇调节元件结合蛋白 1 诱导脂肪生成，该过程由 PKR 样内质网激酶的诱导介导。本研究的数据表明，HCMV 诱导的脂肪生成也受到 ChREBP 诱导的控制，这是参与调节 HCMV 诱导的从头脂肪生成的第二种机制。这些结果表明 ChREBP 在 HCMV 感染中重新编程葡萄糖和脂质代谢中起关键作用。
