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

[Guest guest]

Hepatology. 2011 Jul 25. doi: 10.1002/hep.24575. [Epub ahead of print]

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-â 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-á 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.).

Copyright © 2011 American Association for the Study of Liver Diseases.

PMID: 21793032 [PubMed - as supplied by publisher]

[Guest guest]

Hepatology. 2011 Jul 25. doi: 10.1002/hep.24575. [Epub ahead of print]

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-â 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-á 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.).

Copyright © 2011 American Association for the Study of Liver Diseases.

PMID: 21793032 [PubMed - as supplied by publisher]