葡萄糖對於大多數的細胞而言，都是主要、必需、且易於使用的資源；葡萄糖的代謝可以提供細胞碳源以合成相關大分子，如蛋白質、脂肪酸、核苷酸…等。登革病毒為絕對細胞內寄生的病原體，需要利用宿主提供資源去支持病毒的複製；因此，葡萄糖這個細胞中最基本的代謝資源很可能是登革病毒所利用的目標。我們的研究發現，登革病毒感染時會增加細胞使用葡萄糖時的產酸變化量，並且增加細胞對於單醣的攝取。當限制葡萄糖的供給、攝取、進入糖解作用代謝均能抑制登革病毒的感染；在我們不給予醣類或是給予單醣類似物影響葡萄糖使用時，可以觀察到登革病毒醣基蛋白prM、E、與NS1均無法被醣基化。在以糖解作用產物—丙酮酸作為碳源供給的狀況下，登革病毒蛋白醣基化似乎影響登革病毒的成熟或是釋放。此外，我們發現糖解作用的一個重要分支代謝—五碳糖磷酸路徑也是登革病毒感染所需的代謝路徑：缺乏或抑制五碳糖磷酸路徑上的相關酵素，亦可抑制登革病毒。總結而論，我們的研究初步瞭解登革病毒如何利用葡萄糖進行本身的複製，也發現了抑制葡萄糖代謝路徑具有有抑制登革病毒感染的效果，這些結果亦有助於未來登革病毒感染的治療策略開發。

Glucose are major and essential resources for most living organisms. Glucose metabolites provide carbon sources supplying synthesis of macromolecules, such as proteins, fatty acids, and nucleotides. As an obligate intracellular pathogen, dengue virus (DENV) needs to employ host metabolic system to provide these building blocks for its replication. Therefore, DENV may utilize glucose metabolism, the simplest metabolism in host cell, for viral replication. Here we found that the extracellular acidification rate was increased in A549 cells infected with DENV and in Huh7 cells harboring DENV replicon by glucose refueling. Consistently, DENV infection increased the uptake of extracellular 2-NBDG, a green fluorescent glucose analog, indicating the glycolysis pathway is upregulated by DENV. With metabolic inhibitors, DENV titer was reduced by chemicals targeting glycolysis, pentose phosphate pathway (PPP) and aerobic respiration pathway. In the absence of glucose supplement, DENV titer was reduced in culture supernatant and the glycosylation of DENV glycoprotein was suppressed in infected cell lysates. By supplying with the glycolysis product pyruvate, we found that glycosylation may impact on the release or maturation of DENV particle. Moreover, we found that DENV RNA replication was reduced by inhibiting or silencing glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of PPP. In conclusion, our data revealed how DENV accomplishes its replication by employing host glucose metabolism for viral RNA replication and protein glycosylation.

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