Next Article in Journal
The Dual Role of Exosomes in Hepatitis A and C Virus Transmission and Viral Immune Activation
Previous Article in Journal
Development of Phage Lysin LysA2 for Use in Improved Purity Assays for Live Biotherapeutic Products
Article Menu

Export Article

Open AccessArticle
Viruses 2015, 7(12), 6689-6706; doi:10.3390/v7122966

Glucose-6-Phosphate Dehydrogenase Enhances Antiviral Response through Downregulation of NADPH Sensor HSCARG and Upregulation of NF-κB Signaling

1
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Tao-yuan 333, Taiwan
2
Healthy Aging Research Center, Chang Gung University, Tao-yuan 333, Taiwan
3
Department of Laboratory Medicine, Chang Gung Memorial Hospital, Lin-Kou 333, Taiwan
4
Molecular Medicine Research Center, Chang Gung University, Tao-yuan 333, Taiwan
5
Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-yuan 333, Taiwan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Curt Hagedorn
Received: 7 October 2015 / Revised: 7 December 2015 / Accepted: 10 December 2015 / Published: 17 December 2015
(This article belongs to the Section Antivirals & Vaccines)
View Full-Text   |   Download PDF [3441 KB, uploaded 17 December 2015]   |  

Abstract

Glucose-6-phosphate dehydrogenase (G6PD)-deficient cells are highly susceptible to viral infection. This study examined the mechanism underlying this phenomenon by measuring the expression of antiviral genes—tumor necrosis factor alpha (TNF-α) and GTPase myxovirus resistance 1 (MX1)—in G6PD-knockdown cells upon human coronavirus 229E (HCoV-229E) and enterovirus 71 (EV71) infection. Molecular analysis revealed that the promoter activities of TNF-α and MX1 were downregulated in G6PD-knockdown cells, and that the IκB degradation and DNA binding activity of NF-κB were decreased. The HSCARG protein, a nicotinamide adenine dinucleotide phosphate (NADPH) sensor and negative regulator of NF-κB, was upregulated in G6PD-knockdown cells with decreased NADPH/NADP+ ratio. Treatment of G6PD-knockdown cells with siRNA against HSCARG enhanced the DNA binding activity of NF-κB and the expression of TNF-α and MX1, but suppressed the expression of viral genes; however, the overexpression of HSCARG inhibited the antiviral response. Exogenous G6PD or IDH1 expression inhibited the expression of HSCARG, resulting in increased expression of TNF-α and MX1 and reduced viral gene expression upon virus infection. Our findings suggest that the increased susceptibility of the G6PD-knockdown cells to viral infection was due to impaired NF-κB signaling and antiviral response mediated by HSCARG. View Full-Text
Keywords: G6PD; NADPH; coronavirus; enterovirus; antiviral response; HSCARG G6PD; NADPH; coronavirus; enterovirus; antiviral response; HSCARG
Figures

Figure 1

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. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Wu, Y.-H.; Chiu, D.T.-Y.; Lin, H.-R.; Tang, H.-Y.; Cheng, M.-L.; Ho, H.-Y. Glucose-6-Phosphate Dehydrogenase Enhances Antiviral Response through Downregulation of NADPH Sensor HSCARG and Upregulation of NF-κB Signaling. Viruses 2015, 7, 6689-6706.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top