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BioMed Research International
Volume 2017, Article ID 3519158, 14 pages
Research Article

XBP1-Mediated BiP/GRP78 Upregulation Copes with Oxidative Stress in Mosquito Cells during Dengue 2 Virus Infection

1Department of Public Health and Parasitology, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan
2Graduate Institute of Biomedical Sciences, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan
3Environmental Health Department, Banjarnegara Polytechnic, Central Java, Indonesia
4Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Kwei-San, Tao-Yuan, Taiwan
5Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Children’s Hospital, Chang Gung University College of Medicine, Kwei-San, Tao-Yuan, Taiwan

Correspondence should be addressed to Wei-June Chen; wt.ude.ugc.liam@nehcjw

Received 3 June 2017; Revised 1 August 2017; Accepted 23 August 2017; Published 1 October 2017

Academic Editor: Hong-Lin Su

Copyright © 2017 Tien-Huang Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Dengue viruses (DENVs) cause dengue fever which is an important mosquito-borne disease in tropical areas. Generally, DENV does not cause cellular damage in mosquito cells. However, alterations in cytosolic calcium ions ([Ca2+]cyt) and the mitochondrial membrane potential (MMP), as well as accumulated reactive oxygen species (ROS), including superoxide anions () and hydrogen peroxide (H2O2), can be detected in C6/36 cells with DENV2 infection. Evident upregulation of BiP/GRP78 also appeared at 24 h postinfection in DENV2-infected C6/36 cells. As expression of BiP/GRP78 mRNA was reduced when the transcription factor X-box-binding protein-1 (XBP1) was knocked down in C6/36 cells, it demonstrated that BiP/GRP78 is the target gene regulated by the XBP1 signal pathway. We further demonstrated that the expression and splicing activity of XBP1 were upregulated in parallel with DENV2 infection in C6/36 cells. In C6/36 cells with BiP/GRP78 overexpression, oxidative stress indicators including [Ca2+]cyt, MMP, , and H2O2 were all pushed back to normal. Taken together, DENV2 activates XBP1 at earlier stage of infection, followed by upregulating BiP/GRP78 in mosquito cells. This regulatory pathway contributes a cascade in relation to oxidative stress alleviation. The finding provides insights into elucidating how mosquitoes can healthily serve as a vector of arboviruses in nature.