Hyperglycemia exacerbates dengue virus infection by facilitating poly(A)-binding protein–mediated viral translation

Ting Jing Shen, Chia Ling Chen, Tsung Ting Tsai, Ming Kai Jhan, Chyi Huey Bai, Yu Chun Yen, Ching Wen Tsai, Cheng Yi Lee, Po Chun Tseng, Chia Yi Yu, Chiou Feng Lin

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)


Diabetes mellitus (DM) is highly comorbid with severe dengue diseases; however, the underlying mechanisms are unclear. Patients with DM have a 1.61-fold increased risk of developing dengue hemorrhagic fever. In search of host factors involved in dengue virus (DENV) infection, we used high-glucose (HG) treatment and showed that HG increased viral protein expression and virion release but had no effects on the early stages of viral infection. After HG stimulation, DENV–firefly luciferase–transfected assay and cellular replicon–based assay indicated increased viral translation, whereas using the glucose uptake inhibitor phloretin blocked this effect. HG treatment increased the translational factor poly(A)-binding protein (PABP) in a glucose transporter–associated, PI3K/ AKT-regulated manner. Silencing PABP significantly decreased HG-prompted virion production. HG enhanced the formation of the PABP–eukaryotic translation initiation factor 4G complex, which is regulated by protein–disulfide isomerase. Hyperglycemia increased PABP expression, mortality rate, viral protein expression, and viral loads in streptozotocin-induced DM mice. Overall, hyperglycemic stress facilitates DENV infection by strengthening PABP-mediated viral translation.
期刊JCI insight
出版狀態已發佈 - 11月 8 2022

ASJC Scopus subject areas

  • 醫藥 (全部)


深入研究「Hyperglycemia exacerbates dengue virus infection by facilitating poly(A)-binding protein–mediated viral translation」主題。共同形成了獨特的指紋。