(01-10-11) Vitamin-D: An innate antiviral agent suppressing Hepatitis C virus in human hepatocytes.

Gal-Tanamy M, Bachmetov L, Ravid A, Koren R, Erman A, Tur-Kaspa R, Zemel R.
Source
Molecular Hepatology Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University.
Abstract
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-D(3) remarkably inhibits HCV production in Huh7.5 hepatoma cells. These cells express CYP27B1, the gene encoding for the enzyme responsible for the synthesis of the vitamin-D hormonally active metabolite, calcitriol. Treatment with vitamin-D(3) resulted in calcitriol production and induction of calcitriol target gene CYP24A1, indicating that these cells contain the full machinery for vitamin-D metabolism and activity. Notably, treatment with calcitriol resulted in HCV inhibition. Collectively, these findings suggest that vitamin-D(3) has an anti-viral activity which is mediated by its active metabolite. This anti-viral activity involves the induction of interferon signaling pathway resulting in expression of interferon-? and the interferon-stimulated gene, MxA. Intriguingly, HCV infection increased calcitriol production by inhibiting CYP24A1 induction, the enzyme responsible for the first step in calcitriol catabolism. Importantly, the combination of vitamin-D(3) or calcitriol and interferon-? synergistically inhibited viral production. Conclusion: This study demonstrates for the first time a direct anti-viral effect of vitamin-D in an in-vitro infectious virus production system. It proposes an interplay between the hepatic vitamin-D endocrine system and HCV, suggesting that vitamin-D has a role as natural anti-viral mediator. Importantly, our study implies that vitamin-D might have an interferon sparing effect thus improving antiviral treatment of HCV-infected patients. (HEPATOLOGY 2011.).

Source: Hepatology. 2011 Jul 25

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