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

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 (H...

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Autores principales: Shen, Ting-Jing, Chen, Chia-Ling, Tsai, Tsung-Ting, Jhan, Ming-Kai, Bai, Chyi-Huey, Yen, Yu-Chun, Tsai, Ching-Wen, Tseng, Po-Chun, Yu, Chia-Yi, Lin, Chiou-Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9675471/
https://www.ncbi.nlm.nih.gov/pubmed/36125898
http://dx.doi.org/10.1172/jci.insight.142805
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author Shen, Ting-Jing
Chen, Chia-Ling
Tsai, Tsung-Ting
Jhan, Ming-Kai
Bai, Chyi-Huey
Yen, Yu-Chun
Tsai, Ching-Wen
Tseng, Po-Chun
Yu, Chia-Yi
Lin, Chiou-Feng
author_facet Shen, Ting-Jing
Chen, Chia-Ling
Tsai, Tsung-Ting
Jhan, Ming-Kai
Bai, Chyi-Huey
Yen, Yu-Chun
Tsai, Ching-Wen
Tseng, Po-Chun
Yu, Chia-Yi
Lin, Chiou-Feng
author_sort Shen, Ting-Jing
collection PubMed
description 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.
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spelling pubmed-96754712022-11-21 Hyperglycemia exacerbates dengue virus infection by facilitating poly(A)-binding protein–mediated viral translation Shen, Ting-Jing Chen, Chia-Ling Tsai, Tsung-Ting Jhan, Ming-Kai Bai, Chyi-Huey Yen, Yu-Chun Tsai, Ching-Wen Tseng, Po-Chun Yu, Chia-Yi Lin, Chiou-Feng JCI Insight Research Article 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. American Society for Clinical Investigation 2022-11-08 /pmc/articles/PMC9675471/ /pubmed/36125898 http://dx.doi.org/10.1172/jci.insight.142805 Text en © 2022 Shen et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Shen, Ting-Jing
Chen, Chia-Ling
Tsai, Tsung-Ting
Jhan, Ming-Kai
Bai, Chyi-Huey
Yen, Yu-Chun
Tsai, Ching-Wen
Tseng, Po-Chun
Yu, Chia-Yi
Lin, Chiou-Feng
Hyperglycemia exacerbates dengue virus infection by facilitating poly(A)-binding protein–mediated viral translation
title Hyperglycemia exacerbates dengue virus infection by facilitating poly(A)-binding protein–mediated viral translation
title_full Hyperglycemia exacerbates dengue virus infection by facilitating poly(A)-binding protein–mediated viral translation
title_fullStr Hyperglycemia exacerbates dengue virus infection by facilitating poly(A)-binding protein–mediated viral translation
title_full_unstemmed Hyperglycemia exacerbates dengue virus infection by facilitating poly(A)-binding protein–mediated viral translation
title_short Hyperglycemia exacerbates dengue virus infection by facilitating poly(A)-binding protein–mediated viral translation
title_sort hyperglycemia exacerbates dengue virus infection by facilitating poly(a)-binding protein–mediated viral translation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9675471/
https://www.ncbi.nlm.nih.gov/pubmed/36125898
http://dx.doi.org/10.1172/jci.insight.142805
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