Characteristics of CpG Islands and their quasispecies of full-length hepatitis B virus genomes from patients at different phases of infection

Xue, Yuan; Wang, Mingjie; Huang, Su-Yuan; Yang, Zhitao; Yu, Demin; Han, Yue; Zhu, Mingyu; Huang, Danqing; Zhang, Donghua; Gong, Qiming; Zhang, Xinxin

doi:10.1186/s40064-016-3192-3

Cited by 5 publications

(10 citation statements)

References 32 publications

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“…Here, we analysed the PreC/C and PreS/S genes of nine and 13 isolates respectively for CpG islands. CpG islands identified in PreS/S and PreC/C genes were designated II and III respectively as previously described [22]. As shown in Supplementary Table1, one (7.6 %) and four (44.44 %) of PreS/S and PreC/C genes of the isolates had CpG islands in that order.…”

Section: Resultsmentioning

confidence: 99%

“…Most proximal and distal sites of the CpG islands were designated start and end respectively. CpG islands were defined according to previously defined criteria: GC content of ≥50 %, observed-sequence longer than 100 bp and a distribution length to expected CpG dinucleotide ratio of ≥0.60 [22,23,26].…”

Section: Cpg Islands Analysismentioning

confidence: 99%

“…Persistence of HBV in liver cells increases the risk of HCC [24,25]. DNA methylation, which occurs in CpG islands, have been described as a pathway through which HBV infection persists in cells thereby leading to chronic, occult and poor prognosis of HBV infection [22,[42][43][44]. The distribution of CpG islands in the context of HBV genotype E have not been previously described despite availability of data for other HBV genotypes [23,26].…”

Section: Association Of Cpg Islands In Prec/c Region With Observed Mumentioning

confidence: 99%

“…Studies have recently associated DNA methylation with the regulation of viral gene expression [22,23]. Through this process, viral oncogenes can persist within and without of genomes.…”

Section: Introductionmentioning

confidence: 99%

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Profiles of mutations in hepatitis B virus surface and polymerase genes isolated from treatment-naïve Nigerians infected with genotype E

Olusola

Faneye

Oluwasemowo

et al. 2021

Journal of Medical Microbiology

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Introduction. Hepatitis B virus (HBV) infection is the leading cause of hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). HBV genotype E (HBV/E) is the predominant genotype in West Africa and has been linked epidemiologically with chronic and occult HBV infections as well as development of HCC. Mutations in the surface and polymerase genes of HBV have been associated with occult infection, drug resistance, vaccine escape, as well as HCC. Hypothesis/Gap Statement. There is limited data on the occurrence and patterns of mutations associated with occult infection, drug resistance, vaccine escape and HCC for HBV/E. Aim. This study characterized amino acid (aa) substitutions in the major hydrophilic (MHR) and reverse transcriptase (RT) regions of the surface and polymerase genes respectively of HBV sequences from a group of Nigerians with genotype E infection. The CpG islands of the PreC/C and PreS/S regions of these sequences were also described. Methodology. HBV surface and polymerase genes were detected using PCR techniques. Occurrence of new and previously described mutations in these genes were analysed using phylogenetic techniques. Results. Overall 13 HBV isolates were each sequenced for polymerase and surface genes mutations. Thirteen and nine PreS/S and PreC/C HBV genes respectively were analysed for CpG islands. Mutations in the MHR and a-determinants region of the S protein were discovered in eleven and nine of the 13 tested isolates respectively. These mutations were concomitant with aa changes in the RT functional domains of the isolates. Mutations associated with vaccine escape, occult infection and poor HCC prognosis were identified in HBV/E isolated in this study. Furthermore, all the isolates had at least one putative nucleotide analogue resistance mutations. Drug resistance mutations had the highest association with CpG islands. Conclusion. The results of this study contribute to further understanding of HBV variability in Nigeria and the West African region. This will aid the planning of adequate HBV immunization and treatment programmes for the countries in the region.

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Section: Resultsmentioning

confidence: 99%

Section: Cpg Islands Analysismentioning

confidence: 99%

Section: Association Of Cpg Islands In Prec/c Region With Observed Mumentioning

confidence: 99%

“…Studies have recently associated DNA methylation with the regulation of viral gene expression [22,23]. Through this process, viral oncogenes can persist within and without of genomes.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Profiles of mutations in hepatitis B virus surface and polymerase genes isolated from treatment-naïve Nigerians infected with genotype E

Olusola

Faneye

Oluwasemowo

et al. 2021

Journal of Medical Microbiology

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“…Furthermore, certain viral haplotypes that adapt to the pressure changes gradually become predominant due to the competitive replication[ 9 ]. The evolution of HBV QS has been studied in various serum samples[ 10–13 ]; however, the liver is the organ specifically infected by HBV, hence, HBV QS in the liver better reflects the truth than that in the serum. Recently, the characteristic of HBV QS in the liver tissues of patients with HCC has been investigated, wherein the QS heterogeneity across the HBV PreS region or core promoter region between tumour and adjacent non-tumour tissues was observed[ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Compartmentalisation of Hepatitis B virus X gene evolution in hepatocellular carcinoma microenvironment and the genotype-phenotype correlation of tumorigenicity in HBV-related patients with hepatocellular carcinoma

Fang

Guo

et al. 2022

Emerging Microbes & Infections

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Hepatitis B virus (HBV) exists as quasispecies (QS). However, the evolutionary characteristics of haplotypes of HBV X gene in the hepatocellular carcinoma (HCC) microenvironment remain unclear. Mutations across X gene are essential for the tumorigenicity of HBV X protein (HBx). However, the functional phenotypes of many mutant HBx remain unknown. This study aims to compare the characteristics of X gene evolution between tumour and non-tumour tissues in HCC patients and investigate the tumorigenic phenotype of HBx harbouring mutation T81P/S101P/L123S. This study included 24 HCC patients. Molecular cloning of X gene was performed to analyse characteristics of haplotypes in liver tissues. HCC cell lines stably expressing wild-type or mutant HBx and subcutaneous tumour xenograft mouse model were used to assess HBx-T81P/S101P/L123S tumorigenicity. The mean heterogeneity of HBV QS across X gene in tumour tissues was lower than that in non-tumour tissues. A location bias was observed in X gene clones with genotype C or D in tumour tissues compared to those with genotype B. Mutations in genotype-C or – D clones were mainly clustered in the dimerization region and aa110-aa140 within the transactivation region. A novel mutation combination at residues 81, 101 and 123 was identified in tumour tissues. Further, HBx-T81P/S101P/L123S promotes cell proliferation and increases genomic instability, which was mediated by MYC. This study elucidates the compartmentalized evolution patterns of HBV X gene between intra tumour and non-tumour tissues in HCC patients and provides a new mechanism underlying HBV-driven hepatocarcinogenesis, suggesting a potential viral marker for monitoring HCC.

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Hepatitis B virus DNA methylation and its potential role in chronic hepatitis B

Low

Ngeow

Chook

et al. 2022

Expert Rev. Mol. Med.

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Hepatitis B virus (HBV) infection led to 66% liver deaths world-wide in year 2015. Thirty-seven per cent of these deaths were the result of chronic hepatitis B (CHB)-associated hepatocellular carcinoma (HCC). Although early diagnosis of HCC improves survival, early detection is rare. Methylation of HBV DNA including covalently closed circular DNA (cccDNA) is more often encountered in HCC cases than those in CHB and cirrhosis. Three typical CpG islands within the HBV genome are the common sites for methylation. The HBV cccDNA methylation affects the viral replication and protein expression in the course of infection and may associate with the disease pathogenesis and HCC development. We review the current findings in HBV DNA methylation that provide insights into its role in HCC diagnosis.

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Characteristics of CpG Islands and their quasispecies of full-length hepatitis B virus genomes from patients at different phases of infection

Cited by 5 publications

References 32 publications

Profiles of mutations in hepatitis B virus surface and polymerase genes isolated from treatment-naïve Nigerians infected with genotype E

Profiles of mutations in hepatitis B virus surface and polymerase genes isolated from treatment-naïve Nigerians infected with genotype E

Compartmentalisation of Hepatitis B virus X gene evolution in hepatocellular carcinoma microenvironment and the genotype-phenotype correlation of tumorigenicity in HBV-related patients with hepatocellular carcinoma

Hepatitis B virus DNA methylation and its potential role in chronic hepatitis B

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