25-Hydroxyvitamin D Inhibits Hepatitis C Virus Production in Hepatocellular Carcinoma Cell Line by a Vitamin D Receptor-Independent Mechanism

Autor: Romy Zemel, Assaf Issachar, Arie Erman, Noa Rapaport, Ran Tur-Kaspa, L. Bachmetov, Amiram Ravid
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
hepatitis C virus
Hepacivirus
medicine.disease_cause
Calcitriol receptor
lcsh:Chemistry
chemistry.chemical_compound
0302 clinical medicine
lcsh:QH301-705.5
Spectroscopy
Cholecalciferol
Reverse Transcriptase Polymerase Chain Reaction
25-hydroxyvitamin D3
Liver Neoplasms
vitamin D3
General Medicine
Computer Science Applications
030220 oncology & carcinogenesis
medicine.drug
Vitamin
medicine.medical_specialty
Carcinoma
Hepatocellular
Calcitriol
Cell Survival
Hepatitis C virus
Real-Time Polymerase Chain Reaction
Catalysis
Virus
Article
Inorganic Chemistry
03 medical and health sciences
Internal medicine
Cell Line
Tumor
medicine
Vitamin D and neurology
Humans
vitamin D receptor
Physical and Theoretical Chemistry
Mode of action
Molecular Biology
Calcifediol
Organic Chemistry
030104 developmental biology
Endocrinology
chemistry
lcsh:Biology (General)
lcsh:QD1-999
Receptors
Calcitriol
CRISPR-Cas Systems
Zdroj: International Journal of Molecular Sciences, Vol 20, Iss 9, p 2367 (2019)
International Journal of Molecular Sciences
Volume 20
Issue 9
ISSN: 1422-0067
Popis: Previously, we have reported that the active vitamin D metabolite, calcitriol and vitamin D3 (cholecalciferol), both remarkably inhibit hepatitis C virus production. The mechanism by which vitamin D3 exerts its effect is puzzling due to the low levels of calcitriol produced in vitamin D3-treated Huh7.5 cells. In this study, we aimed to explore the mechanism of vitamin D3 anti-hepatitis C virus effect. We show 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. This is inferred from the findings that 25(OH)D3 could inhibit hepatitis C virus production in our system, and that adequate concentrations needed to exert this effect are produced in Huh7.5 cells treated with vitamin D3. Using the CRISPR-Cas9 editing technology to knockout the vitamin D receptor, we found that the antiviral activity of vitamin D3 and 25(OH)D3 was not impaired in the vitamin D receptor knockout cells. This result indicates that 25(OH)D3 anti-hepatitis C virus effect is exerted by a vitamin D receptor-independent mode of action. The possibility that vitamin D3 and 25(OH)D3, being 3&beta
hydroxysteroids, affect hepatitis C virus production by direct inhibition of the Hedgehog pathway in a vitamin D receptor-independent manner was ruled out. Taken together, this study proposes a novel mode of action for the anti-hepatitis C virus activity of vitamin D3 that is mediated by 25(OH)D3 in a vitamin D receptor-independent mechanism.
Databáze: OpenAIRE
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