PDF(Pubmed)
Abstract：
OBJECTIVE: Viruses modulate host cell metabolism to support the mass production of viral progeny. For human cytomegalovirus, we find that the viral UL38 protein is critical for driving these pro-viral metabolic changes. However, our results indicate that these changes come at a cost, as UL38 induces an anabolic rigidity that leads to a metabolic vulnerability. We find that UL38 decouples the link between glucose availability and fatty acid biosynthetic activity. Normal cells respond to glucose limitation by down-regulating fatty acid biosynthesis. Expression of UL38 results in the inability to modulate fatty acid biosynthesis in response to glucose limitation, which results in cell death. We find this vulnerability in the context of viral infection, but this linkage between fatty acid biosynthesis, glucose availability, and cell death could have broader implications in other contexts or pathologies that rely on glycolytic remodeling, for example, oncogenesis.
摘要：
目的：病毒调节宿主细胞代谢以支持病毒后代的大量生产。对于人类巨细胞病毒，我们发现病毒UL38蛋白对于驱动这些前病毒代谢变化至关重要.然而,我们的结果表明，这些变化是有代价的，因为UL38诱导合成代谢刚性，导致代谢脆弱性。我们发现UL38解耦了葡萄糖利用率和脂肪酸生物合成活性之间的联系。正常细胞通过下调脂肪酸生物合成来响应葡萄糖限制。UL38的表达导致无法调节脂肪酸生物合成以响应葡萄糖限制，导致细胞死亡。我们在病毒感染的背景下发现了这种脆弱性，但是脂肪酸生物合成之间的联系，葡萄糖的可用性，细胞死亡可能在其他依赖糖酵解重塑的环境或病理中产生更广泛的影响，例如,肿瘤发生。
