Calcitriol inhibits HCV infection via blockade of activation of PPAR and interference with endoplasmic reticulum-associated degradation

Yu Min Lin, Hung Yu Sun, Wen Tai Chiu, Hui Chen Su, Yu Chieh Chien, Lee Won Chong, Hung Chuen Chang, Chyi Huey Bai, Kung Chia Young, Chiung Wen Tsao

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Article number57
JournalViruses
Volume10
Issue number2
DOIs
Publication statusPublished - 2018 Feb

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Virology

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