Activation of Nrf2 by the dengue virus causes an increase in CLEC5A, which enhances TNF-α production by mononuclear phagocytes

Yi Lin Cheng, Yee-Shin Lin, Chia Ling Chen, Tsung Ting Tsai, Cheng Chieh Tsai, Yan Wei Wu, Yi Dan Ou, Yu Yi Chu, Ju-Ming Wang, Chia Yi Yu, Chiou Feng Lin

研究成果: Article

16 引文 (Scopus)

摘要

Infection by the dengue virus (DENV) threatens global public health due to its high prevalence and the lack of effective treatments. Host factors may contribute to the pathogenesis of DENV; herein, we investigated the role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which is activated by DENV in mononuclear phagocytes. DENV infection selectively activates Nrf2 following nuclear translocation. Following endoplasmic reticular (ER) stress, protein kinase R-like ER kinase (PERK) facilitated Nrf2-mediated transcriptional activation of C-type lectin domain family 5, member A (CLEC5A) to increase CLEC5A expression. Signaling downstream of the Nrf2-CLEC5A interaction enhances Toll-like receptor 3 (TLR3)-independent tumor necrosis factor (TNF)-α production following DENV infection. Forced expression of the NS2B3 viral protein induces Nrf2 nuclear translocation/activation and CLEC5A expression which increases DENV-induced TNF-α production. Animal studies confirmed Nrf2-induced CLEC5A and TNF-α in brains of DENV-infected mice. These results demonstrate that DENV infection causes Nrf2-regulated TNF-α production by increasing levels of CLEC5A.

原文English
文章編號32000
期刊Scientific reports
6
DOIs
出版狀態Published - 2016 八月 26

指紋

Dengue Virus
Phagocytes
Tumor Necrosis Factor-alpha
Virus Diseases
Toll-Like Receptor 3
C-Type Lectins
Viral Proteins
Protein Kinases
Transcriptional Activation
Public Health
Brain
Infection

All Science Journal Classification (ASJC) codes

  • General

引用此文

Cheng, Yi Lin ; Lin, Yee-Shin ; Chen, Chia Ling ; Tsai, Tsung Ting ; Tsai, Cheng Chieh ; Wu, Yan Wei ; Ou, Yi Dan ; Chu, Yu Yi ; Wang, Ju-Ming ; Yu, Chia Yi ; Lin, Chiou Feng. / Activation of Nrf2 by the dengue virus causes an increase in CLEC5A, which enhances TNF-α production by mononuclear phagocytes. 於: Scientific reports. 2016 ; 卷 6.
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abstract = "Infection by the dengue virus (DENV) threatens global public health due to its high prevalence and the lack of effective treatments. Host factors may contribute to the pathogenesis of DENV; herein, we investigated the role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which is activated by DENV in mononuclear phagocytes. DENV infection selectively activates Nrf2 following nuclear translocation. Following endoplasmic reticular (ER) stress, protein kinase R-like ER kinase (PERK) facilitated Nrf2-mediated transcriptional activation of C-type lectin domain family 5, member A (CLEC5A) to increase CLEC5A expression. Signaling downstream of the Nrf2-CLEC5A interaction enhances Toll-like receptor 3 (TLR3)-independent tumor necrosis factor (TNF)-α production following DENV infection. Forced expression of the NS2B3 viral protein induces Nrf2 nuclear translocation/activation and CLEC5A expression which increases DENV-induced TNF-α production. Animal studies confirmed Nrf2-induced CLEC5A and TNF-α in brains of DENV-infected mice. These results demonstrate that DENV infection causes Nrf2-regulated TNF-α production by increasing levels of CLEC5A.",
author = "Cheng, {Yi Lin} and Yee-Shin Lin and Chen, {Chia Ling} and Tsai, {Tsung Ting} and Tsai, {Cheng Chieh} and Wu, {Yan Wei} and Ou, {Yi Dan} and Chu, {Yu Yi} and Ju-Ming Wang and Yu, {Chia Yi} and Lin, {Chiou Feng}",
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Activation of Nrf2 by the dengue virus causes an increase in CLEC5A, which enhances TNF-α production by mononuclear phagocytes. / Cheng, Yi Lin; Lin, Yee-Shin; Chen, Chia Ling; Tsai, Tsung Ting; Tsai, Cheng Chieh; Wu, Yan Wei; Ou, Yi Dan; Chu, Yu Yi; Wang, Ju-Ming; Yu, Chia Yi; Lin, Chiou Feng.

於: Scientific reports, 卷 6, 32000, 26.08.2016.

研究成果: Article

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AU - Lin, Yee-Shin

AU - Chen, Chia Ling

AU - Tsai, Tsung Ting

AU - Tsai, Cheng Chieh

AU - Wu, Yan Wei

AU - Ou, Yi Dan

AU - Chu, Yu Yi

AU - Wang, Ju-Ming

AU - Yu, Chia Yi

AU - Lin, Chiou Feng

PY - 2016/8/26

Y1 - 2016/8/26

N2 - Infection by the dengue virus (DENV) threatens global public health due to its high prevalence and the lack of effective treatments. Host factors may contribute to the pathogenesis of DENV; herein, we investigated the role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which is activated by DENV in mononuclear phagocytes. DENV infection selectively activates Nrf2 following nuclear translocation. Following endoplasmic reticular (ER) stress, protein kinase R-like ER kinase (PERK) facilitated Nrf2-mediated transcriptional activation of C-type lectin domain family 5, member A (CLEC5A) to increase CLEC5A expression. Signaling downstream of the Nrf2-CLEC5A interaction enhances Toll-like receptor 3 (TLR3)-independent tumor necrosis factor (TNF)-α production following DENV infection. Forced expression of the NS2B3 viral protein induces Nrf2 nuclear translocation/activation and CLEC5A expression which increases DENV-induced TNF-α production. Animal studies confirmed Nrf2-induced CLEC5A and TNF-α in brains of DENV-infected mice. These results demonstrate that DENV infection causes Nrf2-regulated TNF-α production by increasing levels of CLEC5A.

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