The metabolic sensors FXRα, PGC‐1 α, and SIRT1 cooperatively regulate hepatitis B virus transcription

@article{Curtil2014TheMS,
  title={The metabolic sensors FXR$\alpha$, PGC‐1 $\alpha$, and SIRT1 cooperatively regulate hepatitis B virus transcription},
  author={Claire Curtil and Liviu Sorin Enache and Pauline Radreau and Anne-Ga{\"e}lle Dron and Caroline Scholt{\`e}s and A. Deloire and Didier Roche and Vincent Lotteau and Patrice Andr{\'e} and Christophe Rami{\`e}re},
  journal={The FASEB Journal},
  year={2014},
  volume={28},
  pages={1454 - 1463}
}
Hepatitis B virus (HBV) genome transcription is highly dependent on liver‐enriched, metabolic nuclear receptors (NRs). Among others, NR farnesoid X receptor a (FXRa) enhances HBV core promoter activity and pregenomic RNA synthesis. Interestingly, two food‐withdrawal‐induced FXRα modulators, peroxisome proliferator‐activated receptor‐γ coactivator 1α (PGC‐1α) and deacetylase SIRT1, have been found to be associated with HBV genomes ex vivo. Whereas PGC‐1α induction was shown to increase HBV… 

Resveratrol enhances HBV replication through activating Sirt1-PGC-1α-PPARα pathway

It is identified that RSV enhances HBV transcription and replication especially acting on the core promoter, which depends on Sirt1-PGC-1α-PPARα pathway, and patients with hepatitis B infection should be cautious taking RSV as a dietary supplement.

Interplay between SIRT1 and hepatitis B virus X protein in the activation of viral transcription.

Farnesoid X receptor‐α is a proviral host factor for hepatitis B virus that is inhibited by ligands in vitro and in vivo

The results suggest that the physiologic balance of FXR α expression and activation by bile acid is a key host metabolic pathway in the regulation of HBV infection and that FXRα can be envisioned as a target for HBV treatment.

Cisplatin Enhances Hepatitis B Virus Replication and PGC-1α Expression through Endoplasmic Reticulum Stress

It is reported that peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 α) plays a central role in cisplatin-induced HBV transcription and replication and pharmacologic inhibition of ER stress impaired PGC-1α upregulation and HBV production induced by cisPlatin treatment.

Reciprocal regulation of farnesoid X receptor α activity and hepatitis B virus replication in differentiated HepaRG cells and primary human hepatocytes

HBV replication and FXR regulation seem to be interdependent, and altered bile salt metabolism homeostasis might contribute to the persistence of HBV infection.

IL6 Inhibits HBV Transcription by Targeting the Epigenetic Control of the Nuclear cccDNA Minichromosome

It is shown that IL6 treatment leads to a reduction of cccDNA-bound histone acetylation paralleled by a rapid decrease in 3.5kb/pgRNA and subgenomic HBV RNAs transcription without affecting cCCDNA chromatinization or ccc DNA levels.

Restitution of gene expression and histone acetylation signatures altered by hepatitis B virus through antiviral microRNA-like molecules in nontransformed murine hepatocytes

It is shown that the expression of several genes and the chromatin landscape become altered upon HBV infection, including global hypoacetylation of H2A.Z and H3K9, which could contribute to the HBV-induced pathomechanism in nontransformed hepatocytes.

Emerging role of silent information regulator 1 (SIRT1) in hepatocellular carcinoma: a potential therapeutic target

The focus of this review was to delineate the carcinogenesis effects of Sirt1 on HCC and present an overview of SIRT1 functions in normal liver followed by SIRT 1 roles in HCC, with focus on the underlying molecular mechanism to promote SIRT2 as a new therapeutic target for HCC.

Farnesoid X receptor agonist for the treatment of chronic hepatitis B: A safety study

Vonafexor was safe with a decline in HBV markers observed in CHB patients suggesting a potential anti‐viral effect the therapeutic potential of which has to be evaluated in larger trials.

References

SHOWING 1-10 OF 43 REFERENCES

PGC-1α controls hepatitis B virus through nutritional signals

It is concluded that HBV is tightly regulated by changes in the body's nutritional state through the metabolic regulator PGC-1α, a major metabolic regulator and a coactivator of key gluconeogenic genes, robustly coactivates HBV transcription.

Peroxisome Proliferator-Activated Receptor γ Coactivator 1α and Small Heterodimer Partner Differentially Regulate Nuclear Receptor-Dependent Hepatitis B Virus Biosynthesis

The effects of PGC1α and SHP on viral biosynthesis in the human hepatoma cell line Huh7 were similar to those observed in the nonhepatoma cells expressing ERRα and ERRγ, suggesting that these nuclear receptors may have a major role in governing HBV transcription and replication in this cell line.

Limited Effects of Fasting on Hepatitis B Virus (HBV) Biosynthesis in HBV Transgenic Mice

Fasting was shown to rather modestly increase the levels of viral proteins, transcripts, and replication intermediates in the HBV transgenic mouse model of chronic viral infection, suggesting that caloric restriction may modulate viremia to some extent during natural infection.

Hepatocyte metabolic signalling pathways and regulation of hepatitis B virus expression

The discovery of the mechanisms by which HBV is controlled by the hepatic metabolic milieu may broaden the understanding of the unique regulation of HBV expression and may also explain the mechanism by whichHBV induces liver pathologies.

Transactivation of the Hepatitis B Virus Core Promoter by the Nuclear Receptor FXRα

The data strongly suggest that FXRα is another member of the nuclear receptor superfamily implicated in the regulation ofHBV core promoter activity and that bile acids could play an important role in the natural history of HBV infection.

Modulation of hepatitis B virus replication and hepatocyte differentiation by MicroRNA‐1

These findings provide a novel perspective on the role of miRNAs in host‐virus interactions in HBV infection and reverse cancer cell phenotype, which is apparently beneficial for HBV replication.

Hepatitis B virus X (HBX) protein upregulates β-catenin in a human hepatic cell line by sequestering SIRT1 deacetylase.

It is proposed that HBX upregulates β-catenin by sequestering SIRT1, which leads to anticancer drug resistance and could be a therapeutic strategy for HBV-related hepatocellular carcinoma.

Peroxisome Proliferator-Activated Receptor-Coactivator 1 ( PGC-1 ) : Transcriptional Coactivator and Metabolic Regulator

PGC-1 constitutes one of the first and clearest examples in which biological programs are chiefly regulated by a transcriptional coactivator in response to environmental stimuli and its control of energy homeostasis suggests that it could be a target for antiobesity or diabetes drugs.