Published January 24, 2023 - More info
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.
Ting-Jing Shen, Chia-Ling Chen, Tsung-Ting Tsai, Ming-Kai Jhan, Chyi-Huey Bai, Yu-Chun Yen, Ching-Wen Tsai, Po-Chun Tseng, Chia-Yi Yu, Chiou-Feng Lin
Original citation: JCI Insight. 2022;7(21):142805. https://doi.org/10.1172/jci.insight.142805
Citation for this corrigendum: JCI Insight. 2023;8(2):168446. https://doi.org/10.1172/jci.insight.168446
Cheng-Yi Lee has requested to be removed from the author list, and the corresponding author has agreed. The revised author list is shown above, and the author and affiliation lists in the PDF and HTML versions have been updated accordingly.