A functional polymorphism in <scp>ADAR</scp>1 gene affects <scp>HB</scp>sAg seroclearance both spontaneously and interferon induced

Wu, Xiaopan; Shi, Weimei; Wu, Jan‐Jan; Zhu, Xilin; Chen, Kangmei; Zheng, Sujun; Li, Zhuo; Duan, Zhongping; Li, Hui; Liu, Ying

doi:10.1111/liv.12444

Cited by 7 publications

(9 citation statements)

References 17 publications

(17 reference statements)

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“…Thus, host genetic polymorphisms, particularly those associated with IFN signaling pathways, may potentially alter the responsiveness to IFN-α therapy. Many studies have evaluated the relationship between the outcome of IFN-α treatment for CHB and host genetics and identified the potential relevance of HLAs, STAT4, vitamin D–related genes, and some ISGs (Tseng et al, 2011; Brouwer et al, 2014; Wu et al, 2014; Jiang et al, 2016a; Thanapirom et al, 2017; Brouwer et al, 2019) ( Table S5 ).…”

Section: Antiviral Efficacy Of Interferon-α or Nucleos(t)ide Analoguesmentioning

confidence: 99%

“…SNPs in JAK-STAT pathway genes and ISGs may contribute to the antiviral effects of IFN-based therapy (Kong et al, 2007; Ren et al, 2011; Wu et al, 2014; Jiang et al, 2016a). OAS3, MxA-88, and STAT4 genes in the IFN signaling pathway may have predictive value for the efficacy of interferons, but further studies are needed to verify this.…”

Section: Antiviral Efficacy Of Interferon-α or Nucleos(t)ide Analoguesmentioning

confidence: 99%

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Host Genetic Determinants of Hepatitis B Virus Infection

et al. 2019

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Chronic hepatitis B virus (HBV) infection is still a major health problem worldwide. Recently, a great number of genetic studies based on single nucleotide polymorphisms (SNPs) and genome-wide association studies have been performed to search for host determinants of the development of chronic HBV infection, clinical outcomes, therapeutic efficacy, and responses to hepatitis B vaccines, with a focus on human leukocyte antigens (HLA), cytokine genes, and toll-like receptors. In addition to SNPs, gene insertions/deletions and copy number variants are associated with infection. However, conflicting results have been obtained. In the present review, we summarize the current state of research on host genetic factors and chronic HBV infection, its clinical type, therapies, and hepatitis B vaccine responses and classify published results according to their reliability. The potential roles of host genetic determinants of chronic HBV infection identified in these studies and their clinical significance are discussed. In particular, HLAs were relevant for HBV infection and pathogenesis. Finally, we highlight the need for additional studies with large sample sizes, well-matched study designs, appropriate statistical methods, and validation in multiple populations to improve the treatment of HBV infection.

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Section: Antiviral Efficacy Of Interferon-α or Nucleos(t)ide Analoguesmentioning

confidence: 99%

Section: Antiviral Efficacy Of Interferon-α or Nucleos(t)ide Analoguesmentioning

confidence: 99%

Host Genetic Determinants of Hepatitis B Virus Infection

et al. 2019

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“…ADAR1 mRNA levels also are lower in persons with chronic hepatitis B compared with healthy individuals. Taken together, these findings suggest an antiviral role for ADAR1 in the context of HBV infection (147,149,150).…”

Section: Hepatitis B Virusmentioning

confidence: 64%

“…The single nucleotide polymorphism rs4845384 in the 5 UTR of the ADAR1 gene is associated with HBV clearance (149,150). The allele rs4845384AA is associated with lower expression of ADAR1 and poorer response to IFN therapy compared with non-AA alleles.…”

Section: Hepatitis B Virusmentioning

confidence: 99%

Adenosine Deaminases Acting on RNA (ADARs) and Viral Infections

2021

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C6 deamination of adenosine (A) to inosine (I) in double-stranded RNA (dsRNA) is catalyzed by a family of enzymes known as ADARs (adenosine deaminases acting on RNA) encoded by three genes in mammals. Alternative promoters and splicing produce two ADAR1 proteins, an interferon-inducible cytoplasmic p150 and a constitutively expressed p110 that like ADAR2 is a nuclear enzyme. ADAR3 lacks deaminase activity. A-to-I editing occurs with both viral and cellular RNAs. Deamination activity is dependent on dsRNA substrate structure and regulatory RNA-binding proteins and ranges from highly site selective with hepatitis D RNA and glutamate receptor precursor messenger RNA (pre-mRNA) to hyperediting of measles virus and polyomavirus transcripts and cellular inverted Alu elements. Because I base-pairs as guanosine instead of A, editing can alter mRNA decoding, pre-mRNA splicing, and microRNA silencing. Editing also alters dsRNA structure, thereby suppressing innate immune responses including interferon production and action. Expected final online publication date for the Annual Review of Virology, Volume 8 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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“…Wu et al (48,49) reported that rs4845384, an SNP in the 5Ј-UTR of the ADAR1 gene, is associated with HBV clearance and ADAR1 promoter activity in vitro. The allele rs4845384A is reportedly associated with a lower expression of ADAR1, and a Figure 6.…”

Section: Adar1 Inhibits Hbv Replication Through Mir-122mentioning

confidence: 99%

Adenosine deaminase acting on RNA-1 (ADAR1) inhibits hepatitis B virus (HBV) replication by enhancing microRNA-122 processing

Liu

Wang

et al. 2019

Journal of Biological Chemistry

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Edited by Charles E. Samuel Adenosine deaminases acting on RNA-1 (ADAR1) involves adenosine to inosine RNA editing and microRNA processing. ADAR1 is known to be involved in the replication of various viruses, including hepatitis C and D. However, the role of ADAR1 in hepatitis B virus (HBV) infection has not yet been elucidated. Here, for the first time, we demonstrated ADAR1 antiviral activity against HBV. ADAR1 has two splicing isoforms in human hepatocytes: constitutive p110 protein and interferon-␣ (IFN-␣)-responsive p150 protein. We found that overexpression of ADAR1 decreased HBV RNA in an HBV culture model. A catalytic-site mutant ADAR1 also decreased HBV RNA levels, whereas another adenosine deaminases that act on the RNA (ADAR) family protein, ADAR2, did not. Moreover, the induction of ADAR1 by stimulation with IFN-␣ also reduced HBV RNA levels. Decreases in endogenous ADAR1 expression by knock-down or knockout increased HBV RNA levels. A major hepatocyte-specific microRNA, miRNA-122, was found to be positively correlated with ADAR1 expression, and exogenous miRNA-122 decreased both HBV RNA and DNA, whereas, conversely, transfection with a miRNA-122 inhibitor increased them. The reduction of HBV RNA by ADAR1 expression was abrogated by p53 knock-down, suggesting the involvement of p53 in the ADAR1-mediated reduction of HBV RNA. This study demonstrated, for the first time, that ADAR1 plays an antiviral role against HBV infection by increasing the level of miRNA-122 in hepatocytes.

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A functional polymorphism in ADAR1 gene affects HBsAg seroclearance both spontaneously and interferon induced

Cited by 7 publications

References 17 publications

Host Genetic Determinants of Hepatitis B Virus Infection

Host Genetic Determinants of Hepatitis B Virus Infection

Adenosine Deaminases Acting on RNA (ADARs) and Viral Infections

Adenosine deaminase acting on RNA-1 (ADAR1) inhibits hepatitis B virus (HBV) replication by enhancing microRNA-122 processing

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