Inhibition of STAT1 methylation is involved in the resistance of hepatitis B virus to Interferon alpha

Li, Jie; Chen, Feng; Zheng, Ming‐Hua; Zhu, Haihong; Zhao, Dongjiu; Liu, Weixia; Liu, Wei; Chen, Zhi

doi:10.1016/j.antiviral.2009.10.011

Cited by 36 publications

(42 citation statements)

References 31 publications

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“…Recent studies have shown that AdoMet can increase the induction of ISGs and the antiviral effects of IFN-␣ by increasing STAT1 methylation, possibly affecting STAT1-DNA binding (31). Inhibition of STAT1 methylation is involved in the resistance of hepatitis B virus to IFN-␣ (18). These studies suggest that AdoMet can restore STAT1 methylation and improve IFN-␣ signaling in vitro.…”

Section: Discussionmentioning

confidence: 71%

“…However, type I IFN receptors were expressed to a much higher extent in HepG2.2.15 cells than in HepG2 cells. Therefore, the potential role of STAT1 methylation remains controversial (18). It is thus necessary to further investigate the effect of the GC-induced increase of AdoMet production on the STAT pathway to obtain a more accurate picture.…”

Section: Discussionmentioning

confidence: 99%

“…Dex-induced Increase of AdoMet Production Restored STAT1 Methylation Rather than Phosphorylation-Recent evidence suggests that HBV has evolved strategies to block the nuclear translocation of STAT1 to limit IFN-␣-induced cellular antiviral responses (18). Because of the crucial role of STAT1 phosphorylation in IFN-␣ signaling, we investigated whether Dex and AdoMet could potentially influence the phosphorylation of STAT1 responding to IFN-␣ in HepG2.2.15.…”

Section: Ifn-␣ Couldmentioning

confidence: 99%

“…We then analyzed the possible epigenetic mechanisms involved. Recent evidence suggests that HBV has evolved strategies to block the nuclear translocation of signal transducers and activators of transcription (STAT1) to limit IFN-␣-induced cellular antiviral responses (18). Furthermore, we explored the effect of the GC-induced increase of AdoMet production on STAT1 methylation and phosphorylation.…”

Section: The Hepatitis B Virus (Hbv)mentioning

confidence: 99%

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Glucocorticoid-induced S-Adenosylmethionine Enhances the Interferon Signaling Pathway by Restoring STAT1 Protein Methylation in Hepatitis B Virus-infected Cells

Bing¹,

Zhu²,

Gao

et al. 2014

Journal of Biological Chemistry

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Background:It is necessary to improve the antiviral response of IFN-␣ for chronic hepatitis B (CHB) patients. Results: Hepatitis B virus (HBV) disrupted glucocorticoid-induced S-adenosylmethionine and methionine adenosyltransferase 1A (MAT1A) expression by hypermethylation within the MAT1A promoter. Conclusion: Glucocorticoid-induced S-adenosylmethionine enhances the response of IFN-␣ by restoring STAT1 methylation in HBV-infected cells. Significance: The combination therapy of glucocorticoids, S-adenosylmethionine, and IFN-␣ is possibly useful for CHB patients.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Ifn-␣ Couldmentioning

confidence: 99%

Section: The Hepatitis B Virus (Hbv)mentioning

confidence: 99%

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Glucocorticoid-induced S-Adenosylmethionine Enhances the Interferon Signaling Pathway by Restoring STAT1 Protein Methylation in Hepatitis B Virus-infected Cells

Bing¹,

Zhu²,

Gao

et al. 2014

Journal of Biological Chemistry

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“…SAMe may improve interferon signaling and antiviral effects through increased methylation of STAT1, resulting in enhanced STAT1-DNA binding and thus greater ISG expression [19]. SAMe is the first interferon sensitizing agent with in vivo efficacy, suggesting its utility as an adjunct to interferon-based therapy; such applications may be particularly important in the era of direct antivirals for HBV infection.…”

Section: Introductionmentioning

confidence: 99%

Feasibility and Efficacy of S-Adenosyl-L-methionine in Patients with HBV-Related HCC with Different BCLC Stages

Guo

et al. 2016

Gastroenterology Research and Practice

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Aims. To understand the feasibility and efficacy of treatment with SAMe in patients with hepatitis B-related HCC with different Barcelona Clinic Liver Cancer (BCLC) stages. Methods. We retrospectively enrolled 697 patients with BCLC early-stage (stages 0-A) and advanced-stage (stages B-C) HCC who underwent SAMe therapy (354 cases) or no SAMe therapy (343 cases). The baseline characteristics, postoperative recoveries, and 24-month overall survival rates of the patients in the 2 groups were compared. Cox regression model analysis was performed to confirm the independent variables influencing the survival rate. Results. For patients in the early-stage (BCLC stages A1–A4) group, little benefit of SAMe therapy was observed. For advanced-stage (BCLC B-C) patients, SAMe therapy reduced alanine aminotransferase (ALT) and aspartate transaminase (AST) levels and effectively delayed the recurrence time and enhanced the 24-month survival rate. Cox regression model analysis in the advanced-stage group revealed that treatment with SAMe, preoperative viral load, and Child-Pugh grade were independent variables influencing survival time. Conclusion. SAMe therapy exhibited protective and therapeutic efficacy for BCLC advanced-stage HBV-related HCC patients. And the efficacy of SAMe therapy should be further explored in randomized prospective clinical trials.

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Higher BST2 Expression Promotes the Anti‐HBV Effect of IFN‐α and BST2 Genetic Variant Predicts PegIFNα Treatment Response of HBeAg‐Positive Chronic Hepatitis B Patients

Chen,

Hou,

et al. 2023

Clin Pharma and Therapeutics

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We previously reported that an interferon (IFN)‐inducible protein, BST2, was regulated by the JAK–STAT pathway activated by CD40, and subsequently suppressing hepatitis B virus (HBV) repliaction and transcription. The current research attempted to assess the impact of BST2 on the IFN‐treated anti‐HBV effect, and explore BST2 variants for predicting pegylated IFN alpha (PegIFNα) therapy response of patients with hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B (CHB). Using an HBV‐transfected cell model, the function of BST2 on HBV DNA replication and transcription driven by IFN was studied. The potentially functional BST2 variants were selected through a strategy of gene‐wide screening. The associations of BST2 variants and polygenic score (PGS) model, which was used to quantify the combined influence of several genetic variants, with treatment response were examined in 2 separate PegIFNα‐treated cohorts of 238 and 707 patients with CHB, respectively. We found that overexpression of BST2 improved the anti‐HBV activity triggered by IFN‐α. Among PegIFNα‐treated patients with CHB, BST2_rs9576 was screened out to be significantly correlated with combined response (CR; i.e., HBeAg seroconversion along with HBV DNA level <3.3log10IU/mL, P = 7.12 × 10−5). Additionally, there was a strong correlation between the PGS incorporating BST2_rs9576 and other 5 genetic variations (previously described predictors of therapy response to PegIFNα) and CR (P = 1.81 × 10−13), hepatitis B surface antigen (HBsAg) level (P = 0.004), as well as HBsAg decline (P = 0.017). In conclusion, higher BST2 expression responded better to IFN‐α treatment. BST2_rs9576 is an effective indicator to forecast therapy response of PegIFNα‐treated patients with CHB. The PGS possesses the potential to boost the ability of PegIFNα therapy response.

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Inhibition of STAT1 methylation is involved in the resistance of hepatitis B virus to Interferon alpha

Cited by 36 publications

References 31 publications

Glucocorticoid-induced S-Adenosylmethionine Enhances the Interferon Signaling Pathway by Restoring STAT1 Protein Methylation in Hepatitis B Virus-infected Cells

Glucocorticoid-induced S-Adenosylmethionine Enhances the Interferon Signaling Pathway by Restoring STAT1 Protein Methylation in Hepatitis B Virus-infected Cells

Feasibility and Efficacy of S-Adenosyl-L-methionine in Patients with HBV-Related HCC with Different BCLC Stages

Higher BST2 Expression Promotes the Anti‐HBV Effect of IFN‐α and BST2 Genetic Variant Predicts PegIFNα Treatment Response of HBeAg‐Positive Chronic Hepatitis B Patients

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