Hepatitis B virus reduced by 5X the Vitamin D getting to liver cells in the lab – Oct 2018

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Hepatitis B VDR reduced Vit D by 5X - Oct 2018

Hepatitis B virus downregulates vitamin D receptor levels in hepatoma cell lines, thereby preventing vitamin D-dependent inhibition of viral transcription and production
Molecular Medicin e201824:53, https://doi.org/10.1186/s10020-018-0055-0
Neta Gotlieb, Irena Tachlytski, Yelena Lapidot, Maya Sultan, Michal Safran and Ziv Ben-Ari

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Background
Vitamin D is a key immune-modulator that plays a role in the innate and adaptive immune systems. Certain pathogens impair the immune defense by downregulating the vitamin D receptor (VDR) pathway. Low serum levels of vitamin D are associated with increased hepatitis B virus (HBV) replication. Our study aimed to assess the in-vitro relationship between HBV production and Vitamin D signaling pathway and to explore the associated mechanism(s).

Methods
HBV transcription and replication was evaluated by qRT-PCR of the HBV-RNA and covalently closed circular DNA (cccDNA). Furthermore, we have transfected the 1.3 X HBV-Luc plasmid to the cells and measured the Luciferase activity using Luminometer. Vitamin D signaling pathway activation was evaluated by measuring the expression levels of VDR, CYP24A1, Tumor necrosis factor α (TNFα) and cathelicidin (CAMP) by qRT-PCR. All assays were performed on HepG2.2.15, HepG2, and HepAD38 cells treated with or without Vitamin D active metabolite: calcitriol.

Results
Calcitriol did not suppress HBV transcription, cccDNA expression or HBV RNA levels in HepG2.2.15 cells. However, VDR transcript levels in HepG2.215 cells were significantly lower compared to HepG2 cells. Similar results were obtained in HepAD38 cell where VDR expression was down-regulated when HBV transcript level was up-regulated. In addition, calcitriol induced VDR-associated signaling, resulting in upregulation of CYP24A1, TNFα and CAMP expression level in HepG2 cells but not in the HepG2.2.15 cells.

Conclusions
These findings indicate that VDR expression is downregulated in HBV-transfected cells, thereby preventing vitamin D from inhibiting transcription and translation of HBV in vitro. HBV might use this mechanism to avoid the immunological defense system by affecting both TNFα and CAMP signaling pathways.

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Poor VDR increases Hepatitis B risk by 1.5 meta-analysis May 2018

Association between vitamin D receptor polymorphisms and hepatitis B virus infection susceptibility: A meta-analysis study.
Gene. 2018 Mar 1;645:105-112. doi: 10.1016/j.gene.2017.12.027. Epub 2017 Dec 14.
He Q1, Huang Y2, Zhang L3, Yan Y4, Liu J4, Song X5, Chen W6.

BACKGROUND:
Hepatitis B virus (HBV) infection is still a serious public health problem. Understanding risk factors associated with development of HBV is greatly important. Numerous studies focus on relationship between vitamin D receptor (VDR) polymorphisms (TaqI, FokI, ApaI, BsmI) and the risk of HBV infection in different ethnic groups. However the results published so far are inconsistent. The aim of this study is to quantify the association between VDR polymorphisms with HBV infection by meta-analysis approach.

METHODS:
A systematic search was performed in Pubmed, Embase, China National Knowledge Infrastructure (CNKI), Database of Chinese Scientific and Technical Periodicals (VIP), and WANFANG. All the relevant studies were published up to October 2016.

RESULTS:
Finally, 15 published studies included 4218 cases and 2298 controls were included in this meta-analysis. It is interesting to note that FokI FF tends to be a risk factor for HBV infection [FF vs. ff: P<0.01, OR (95%CI)=1.54 (1.19-2.00), I2=0.0%], with no heterogeneity.
In addition, genotype Ff and allele F could increase HBV infection risk [Ff vs. ff: P<0.01, OR (95%CI)=1.39 (1.13-1.72); F vs. f: P=0.02, OR (95%CI)=1.23(1.04-1.45)]. However, no associations were found about VDR TaqI, ApaI and BsmI polymorphisms with HBV infection based on each comparison model.

CONCLUSION:
This meta-analysis indicates that FokI genotype FF, Ff and allele F increase the risk of HBV infection. All these results support the notion that VDR FokI genotype might has potential role in HBV susceptibility.