FoxO4 inhibits HBV core promoter activity through ERK-mediated downregulation of HNF4α

Li, Lijie; Li, Yuqi; Xiong, Zhi‐Qi; Shu, Wangqin; Yang, Yuanyuan; Guo, Zhiwei; Gao, Bo

doi:10.1016/j.antiviral.2019.104568

Cited by 9 publications

(20 citation statements)

References 48 publications

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“…4A and B ) and contribute to the reversion of FoxO4-mediated inhibition of rcccDNA transcription and HBV replication ( Fig. 4C and D ), findings which were in agreement with our previous investigation ( 19 ). However, parallel ChIP assays showed that HNF4α expression had little effect on the FoxO4-mediated epigenetic repression of rcccDNA ( Fig.…”

Section: Resultssupporting

confidence: 93%

“…Our previous work showed that FoxO4 inhibited HBV core promoter through the downregulation of HNF4α ( 19 ), and several reports suggested that HNF4α might be involved in epigenetic regulation of target genes ( 25 , 26 ). We therefore explored whether HNF4α participated in the FoxO4-mediated epigenetic suppression of HBV cccDNA.…”

Section: Resultsmentioning

confidence: 99%

“…In terms of HBV infection, it is reported that FoxO1 can promote the transcription and replication of HBV ( 18 ). Our previous study revealed that HBV could significantly downregulate the expression of FoxO4, but not FoxO3 and FoxO1, and that FoxO4 was revealed to inhibit the HBV core promoter activity through ERK1/2-HNF4α axis ( 19 ). Consistent with our investigation, Fu et al ( 20 ) also reported that HBV appeared to suppress FoxO4 expression, and FoxO4 displayed an inhibitory effect on HBV replication.…”

Section: Introductionmentioning

confidence: 99%

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Forkhead O Transcription Factor 4 Restricts HBV Covalently Closed Circular DNA Transcription and HBV Replication through Genetic Downregulation of Hepatocyte Nuclear Factor 4 Alpha and Epigenetic Suppression of Covalently Closed Circular DNA via Interacting with Promyelocytic Leukemia Protein

Gong

et al. 2022

J Virol

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Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Forkhead O Transcription Factor 4 Restricts HBV Covalently Closed Circular DNA Transcription and HBV Replication through Genetic Downregulation of Hepatocyte Nuclear Factor 4 Alpha and Epigenetic Suppression of Covalently Closed Circular DNA via Interacting with Promyelocytic Leukemia Protein

Gong

et al. 2022

J Virol

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“…In preclinical trials, studies demonstrated that MLN4924 could block neddylation and activates the ERK signaling pathway to inhibit the expression of several transcription factors required for HBV replication (Xie et al, 2021), and the Forkhead box O 4 (FoxO4) transcription factor plays an important role in inhibiting HBV core promoter activity through ERK-mediated hepatocyte nuclear factor-4a (HNF4a) down-regulation in vivo (Li et al, 2019a). These agents may provide novel antiviral therapies against HBV infection (Table 2 and Figure 2).…”

Section: Therapeutics That Modulate Ras/ Mek/erk Signaling Pathways T...mentioning

confidence: 99%

Novel Molecular Therapeutics Targeting Signaling Pathway to Control Hepatitis B Viral Infection

Yan

Qiu

Davgadorj

et al. 2022

Front. Cell. Infect. Microbiol.

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Numerous canonical cellular signaling pathways modulate hepatitis B virus (HBV) replication. HBV genome products are known to play a significant role in regulating these cellular pathways for the liver’s viral-related pathology and physiology and have been identified as the main factor in hepatocarcinogenesis. Signaling changes during viral replication ultimately affect cellular persistence, multiplication, migration, genome instability, and genome damage, leading to proliferation, evasion of apoptosis, block of differentiation, and immortality. Recent studies have documented that numerous signaling pathway agonists or inhibitors play an important role in reducing HBV replication in vitro and in vivo, and some have been used in phase I or phase II clinical trials. These optional agents as molecular therapeutics target cellular pathways that could limit the replication and transcription of HBV or inhibit the secretion of the small surface antigen of HBV in a signaling-independent manner. As principle-based available information, a combined strategy including antiviral therapy and immunomodulation will be needed to control HBV infection effectively. In this review, we summarize recent findings on interventions of molecular regulators in viral replication and the interactions of HBV proteins with the components of the various targeting cellular pathways, which may assist in designing novel agents to modulate signaling pathways to prevent HBV replication or carcinogenesis.

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“…NF-κB is an important regulator of inflammation, immunity, or apoptosis and other pathological processes ( Zeisel et al, 2015 ; Li et al, 2019 ; Namineni et al, 2020 ). Activation of NF-κB has been reported to increase the production of pro-inflammatory cytokines.…”

Section: Resultsmentioning

confidence: 99%

A Polysaccharide From Eupolyphaga sinensis Walker With Anti-HBV Activities In Vitro and In Vivo

Zhang

Ding

et al. 2022

Front. Pharmacol.

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Hepatitis B virus (HBV) infection remains a major global threat to human health worldwide. Recently, the Chinese medicines with antiviral properties and low toxicity have been a concern. In our previous study, Eupolyphaga sinensis Walker polysaccharide (ESPS) has been isolated and characterized, while its antiviral effect on HBV remained unclear. The anti-HBV activity of ESPS and its regulatory pathway were investigated in vitro and in vivo. The results showed that ESPS significantly inhibited the production of HBsAg, HBeAg, and HBV DNA in the supernatants of HepG2.2.15 in a dose-dependent manner; HBV RNA and core protein expression were also decreased by ESPS. The in vivo studies using HBV transgenic mice further revealed that ESPS (20 and 40 mg/kg/2 days) significantly reduced the levels HBsAg, HBeAg, and HBV DNA in the serum, as well as HBV DNA and HBV RNA in mice liver. In addition, ESPS activated the Toll-like receptor 4 (TLR4) pathway; elevated levels of IFN-β, TNF-α, and IL-6 in the serum were observed, indicating that the anti-HBV effect of ESPS was achieved by potentiating innate immunity function. In conclusion, our study shows that ESPS is a potential anti-HBV ingredient and is of great value in the development of new anti-HBV drugs.

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FoxO4 inhibits HBV core promoter activity through ERK-mediated downregulation of HNF4α

Cited by 9 publications

References 48 publications

Forkhead O Transcription Factor 4 Restricts HBV Covalently Closed Circular DNA Transcription and HBV Replication through Genetic Downregulation of Hepatocyte Nuclear Factor 4 Alpha and Epigenetic Suppression of Covalently Closed Circular DNA via Interacting with Promyelocytic Leukemia Protein

Forkhead O Transcription Factor 4 Restricts HBV Covalently Closed Circular DNA Transcription and HBV Replication through Genetic Downregulation of Hepatocyte Nuclear Factor 4 Alpha and Epigenetic Suppression of Covalently Closed Circular DNA via Interacting with Promyelocytic Leukemia Protein

Novel Molecular Therapeutics Targeting Signaling Pathway to Control Hepatitis B Viral Infection

A Polysaccharide From Eupolyphaga sinensis Walker With Anti-HBV Activities In Vitro and In Vivo

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