Vitamin D: An innate antiviral agent suppressing hepatitis C virus in human hepatocytes

  title={Vitamin D: An innate antiviral agent suppressing hepatitis C virus in human hepatocytes},
  author={Meital Gal-Tanamy and Larisa Bachmetov and Amiram Ravid and Ruth Koren and Arie Erman and Ran Tur-kaspa and Romy Zemel},
Vitamin D supplementation was reported to improve the probability of achieving a sustained virological response when combined with antiviral treatment against hepatitis C virus (HCV). Our aim was to determine the in vitro potential of vitamin D to inhibit HCV infectious virus production and explore the mechanism(s) of inhibition. Here we show that vitamin D3 remarkably inhibits HCV production in Huh7.5 hepatoma cells. These cells express CYP27B1, the gene encoding for the enzyme responsible for… 
25‐hydroxyvitamin D3 suppresses hepatitis C virus production
25(OH)D3 is a novel anti‐HCV agent that targets an infectious viral particle assembly step and provides insight into the improved efficacy of anti-HCV treatment via the combination of vitamin D3 and IFN.
Inhibition of hepatitis C virus by vitamin D.
25-Hydroxyvitamin D Inhibits Hepatitis C Virus Production in Hepatocellular Carcinoma Cell Line by a Vitamin D Receptor-Independent Mechanism
It is shown that vitamin D3 activity is not mediated by its metabolic conversion to calcitriol, but may be due to its primary metabolic product 25(OH)D3, and proposed a novel mode of action for the anti-hepatitis C virus activity of vitamin D2 that is mediated by 25( OH)D2 in a vitamin D receptor-independent mechanism.
Vitamin D Metabolites Inhibit Hepatitis C Virus and Modulate Cellular Gene Expression.
It is shown that vitamin D reduces HCV protein production in cell culture synergistically with IFN-α and also activates gene expression independently and additively withIFN- α and this may explain its ability to aid in the clearance of HCV in vivo.
Vitamin D Potentiates the Inhibitory Effect of MicroRNA-130a in Hepatitis C Virus Replication Independent of Type I Interferon Signaling Pathway
Calcitriol potentiates the anti-HCV effect of miR-130a in both Con1b replicon and J6/JFH1 culture systems and may contribute to the development of novel anti- HCV therapeutic strategies although the antiviral mechanism needs to be further investigated.
Vitamin D increases the antiviral activity of bronchial epithelial cells in vitro
Vitamin D Receptor and Jak–STAT Signaling Crosstalk Results in Calcitriol-Mediated Increase of Hepatocellular Response to IFN-α
The VDR is identified as a novel suppressor of IFN-α–induced signaling through the Jak–STAT pathway, and silencing of the VDR resulted in an enhanced hepatocellular response to IFn-α.
Calcitriol Inhibits HCV Infection via Blockade of Activation of PPAR and Interference with Endoplasmic Reticulum-Associated Degradation
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.
The importance of vitamin D status in liver histological progression and response to antiviral therapy.
Recent reviews have doubts on any link between vitamin D deficiency and non-skeletal health outcomes, suggesting that vitamin D is not a factor implicated in the pathogenesis of disease (Autier et al 2014).


Vitamin D Decreases Respiratory Syncytial Virus Induction of NF-κB–Linked Chemokines and Cytokines in Airway Epithelium While Maintaining the Antiviral State
It is found that vitamin D decreases the inflammatory response to viral infections in airway epithelium without jeopardizing viral clearance, suggesting that adequate vitamin D levels would contribute to reduced inflammation and less severe disease in RSV-infected individuals.
Distinct Poly(I-C) and Virus-activated Signaling Pathways Leading to Interferon-β Production in Hepatocytes*
It is concluded that hepatocytes contain two distinct antiviral signaling pathways leading to expression of type I IFNs, one dependent upon TLR3 and the other dependent on RIG-I, with little cross-talk between these pathways.
Inhibition of dsRNA-induced signaling in hepatitis C virus-infected cells by NS3 protease-dependent and -independent mechanisms.
Overexpression of individual components of the dsRNA-signaling pathway in HCV-infected and uninfected cells indicates that HCV inhibits IFN- beta promoter activity by inactivating the mitochondrial antiviral signaling protein/IFN-beta promoter stimulator 1 (MAVS/IPS-1), while leaving the IFn-induced Janus kinases-signal transducers and activators of transcription signaling pathway intact.
Vitamin D supplementation improves response to antiviral treatment for recurrent hepatitis C
  • D. Bitetto, C. Fabris, P. Toniutto
  • Medicine
    Transplant international : official journal of the European Society for Organ Transplantation
  • 2011
In conclusion, vitamin D deficiency predicts an unfavourable response to antiviral treatment of RHC and vitamin D supplementation improves the probability of achieving a SVR following antiviral therapy.
Mechanism of action of interferon and ribavirin in treatment of hepatitis C
A better understanding of the mechanism of action of IFN and ribavirin will be essential to optimize current therapeutic strategies and to develop new therapies.
Vitamin D and mucosal immune function
  • Jun Sun
  • Biology, Medicine
    Current opinion in gastroenterology
  • 2010
This review summarizes recent progress in understanding how Vitamin D contributes to mucosal immune function, particularly in relation to the molecular mechanisms by which Vitamin D and VDR influence mucosal immunity, bacterial infection, and inflammation.
Vitamin D and the anti-viral state.
Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon‐based therapy in genotype 1 chronic hepatitis C
Low vitamin D is linked to severe fibrosis and low SVR on interferon (IFN)‐based therapy and G1 CHC patients had low 25(OH)D serum levels, possibly because of reduced CYP27A1 expression.
Type I interferons and the innate immune response--more than just antiviral cytokines.