25-Hydroxyvitamin D3 suppresses hepatitis C virus production

Hepatology. 2012 Oct;56(4):1231-9. doi: 10.1002/hep.25763.


Because the current interferon (IFN)-based treatment for hepatitis C virus (HCV) infection has a therapeutic limitation and side effects, a more efficient therapeutic strategy is desired. Recent studies show that supplementation of vitamin D significantly improves sustained viral response via IFN-based therapy. However, mechanisms and an active molecular form of vitamin D for its anti-HCV effects have not been fully clarified. To address these questions, we infected HuH-7 cells with cell culture-generated HCV in the presence or absence of vitamin D(3) or its metabolites. To our surprise, 25-hydroxyvitamin D(3) [25(OH)D(3) ], but not vitamin D(3) or 1,25-dihydroxyvitamin D(3) , reduced the extra- and intracellular levels of HCV core antigen in a concentration-dependent manner. Single-cycle virus production assay with a CD81-negative cell line reveals that the inhibitory effect of 25(OH)D(3) is at the level of infectious virus assembly but not entry or replication. Long-term 25(OH)D(3) treatment generates a HCV mutant with acquired resistance to 25(OH)D(3) , and this mutation resulting in a N1279Y substitution in the nonstructural region 3 helicase domain is responsible for the resistance.

Conclusion: 25(OH)D(3) is a novel anti-HCV agent that targets an infectious viral particle assembly step. This finding provides insight into the improved efficacy of anti-HCV treatment via the combination of vitamin D(3) and IFN. Our results also suggest that 25(OH)D(3) , not vitamin D(3) , is a better therapeutic option in patients with hepatic dysfunction and reduced enzymatic activity for generation of 25(OH)D(3) .

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Calcifediol / pharmacology*
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cholecalciferol / pharmacology*
  • Dose-Response Relationship, Drug
  • Hepacivirus / drug effects*
  • Hepacivirus / growth & development
  • Hepatitis C / drug therapy
  • Hepatitis C / virology
  • Hepatocytes / drug effects
  • Hepatocytes / immunology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / pharmacology
  • Polyethylene Glycols / pharmacology
  • Polymerase Chain Reaction / methods
  • RNA, Viral / drug effects
  • RNA, Viral / metabolism
  • Recombinant Proteins / pharmacology
  • Ribavirin / pharmacology
  • Sampling Studies
  • Sensitivity and Specificity


  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Cholecalciferol
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2b
  • Calcifediol