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Viruses 2018, 10(2), 57; doi:10.3390/v10020057

Calcitriol Inhibits HCV Infection via Blockade of Activation of PPAR and Interference with Endoplasmic Reticulum-Associated Degradation

1
Department of Gastroenterology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan
2
Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
3
Department of Biomedical Engineering, College of Engineering, National Cheng Kung University, Tainan 70101, Taiwan
4
Department of Pharmacy, Chi-Mei Medical Center, Tainan 71004, Taiwan
5
Department of Long Term Care, Chung Hwa University of Medical Technology, Tainan 71703, Taiwan
6
Department of Public Health, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
*
Author to whom correspondence should be addressed.
Received: 27 November 2017 / Revised: 17 January 2018 / Accepted: 26 January 2018 / Published: 30 January 2018
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Abstract

Vitamin D has been identified as an innate anti-hepatitis C virus (HCV) agent but the possible mechanisms for this issue remain unclear. Here, we clarified the mechanisms of calcitriol-mediated inhibition of HCV infection. Calcitriol partially inhibited HCV infection, nitric oxide (NO) release and lipid accumulation in Huh7.5 human hepatoma cells via the activation of vitamin D receptor (VDR). When cells were pretreated with the activators of peroxisome proliferator-activated receptor (PPAR)-α (Wy14643) and -γ (Ly171883), the calcitriol-mediated HCV suppression was reversed. Otherwise, three individual stimulators of PPAR-α/β/γ blocked the activation of VDR. PPAR-β (linoleic acid) reversed the inhibition of NO release, whereas PPAR-γ (Ly171883) reversed the inhibitions of NO release and lipid accumulation in the presence of calcitriol. The calcitriol-mediated viral suppression, inhibition of NO release and activation of VDR were partially blocked by an inhibitor of endoplasmic reticulum-associated degradation (ERAD), kifunensine. Furthermore, calcitriol blocked the HCV-induced expressions of apolipoprotein J and 78 kDa glucose-regulated protein, which was restored by pretreatment of kifunensine. These results indicated that the calcitriol-mediated HCV suppression was associated with the activation of VDR, interference with ERAD process, as well as blockades of PPAR, lipid accumulation and nitrative stress. View Full-Text
Keywords: calcitriol; hepatitis C virus infection; peroxisome proliferator-activated receptor; endoplasmic reticulum-associated degradation; nitrative stress calcitriol; hepatitis C virus infection; peroxisome proliferator-activated receptor; endoplasmic reticulum-associated degradation; nitrative stress
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MDPI and ACS Style

Lin, Y.-M.; Sun, H.-Y.; Chiu, W.-T.; Su, H.-C.; Chien, Y.-C.; Chong, L.-W.; Chang, H.-C.; Bai, C.-H.; Young, K.-C.; Tsao, C.-W. Calcitriol Inhibits HCV Infection via Blockade of Activation of PPAR and Interference with Endoplasmic Reticulum-Associated Degradation. Viruses 2018, 10, 57.

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