Cytotoxic T lymphocyte responses and CTL epitope escape mutation in HBsAg, anti-HBe positive individuals

Khakoo, Salim I.; Ling, Roger; Scott, Iain; Dodi, Anthony I.; Harrison, Tim J.; Dusheiko, G.; Madrigal, J.A.

doi:10.1136/gut.47.1.137

Cited by 23 publications

(16 citation statements)

References 38 publications

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“…HLA-A*68 alleles have previously been reported to present peptides from influenza and hepatitis B virus [44,45] and squamous cell carcinoma of the lungs [46]. The HLA-A*68 allele group has a valine residue at amino acid position 245 in a region of the a3 domain that is critical for its interaction with the CD8 molecule, whereas all other HLA-A alleles have an alanine residue instead.…”

Section: Discussionmentioning

confidence: 99%

Influence of HLA Alleles on Shedding of Kaposi Sarcoma–Associated Herpesvirus in Saliva in an African Population

et al. 2007

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Section: Discussionmentioning

confidence: 99%

Influence of HLA Alleles on Shedding of Kaposi Sarcoma–Associated Herpesvirus in Saliva in an African Population

et al. 2007

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“…The core protein of HBV is the major target for the antiviral immune response (20). It contains CTL epitopes, T-helper cell epitopes, and B-cell recognition sites (21)(22)(23). Although a variety of mutations may emerge in C genes during the immune clearance phase, only a few mutations within or flanking the HBcAg epitopes have been reported to be of clinical relevance (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

Comparison Study on the Complete Sequence of Hepatitis B Virus Identifies New Mutations in Core Gene Associated with Hepatocellular Carcinoma

Zhu

Yan

Guo

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Mutations in the hepatitis B virus (HBV) genome may influence the activity of liver disease. The aim of this study was to identify new viral variations associated with hepatocellular carcinoma (HCC).Methods: We carried out a comparison study on the complete sequence of HBV isolated from 20 HCC and 35 non-HCC patients in Qidong, China, an area with a high incidence of HCC. We compared the HBV sequences in a consecutive series of plasma samples from four HCC cases before and after the occurrence of HCC. In addition, we selected four mutations in the HBV core (C) gene to verify their relationships to HCC in an independent set of 103 HCC cases and 103 sex-and age-matched non-HCC controls.Results: The pre-S deletion and 12 point mutations, namely, the pre-S2 start codon mutation, T53C in the pre-S2 gene, T766A in the S gene, G1613A, C1653T, A1762T, G1764A in the X gene, and G1899A, C2002T, A2159G, A2189C, and G2203W (A or T) in the pre-C/C gene, showed close associations with HCC. In the validation study, A2159G, A2189C, and G2203W showed consistent associations with HCC by univariate analysis. Multivariate analysis showed that A2189C and G2203W were independent risk factors for HCC. The odds ratios (95% confidence interval) were 3.99 (1.61-9.92) and 9.70 (1.17-80.58), respectively, for A2189C and G2203W.Conclusions: These results implicate A2189C and G2203W as new predictive markers for HCC. Impact: The complete genome analysis of HBV provided pilot data for the identification of novel mutations that could serve as markers for HCC. Cancer Epidemiol Biomarkers Prev; 19(10); 2623-30. ©2010 AACR.

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“…Associations between HLA class I genotypes/alleles and escape mutations in the HBV core gene have been investigated in chronic HBV infection (40,41). However, associations of HLA-DP polymorphisms with HBV mutations have not been reported.…”

Section: Discussionmentioning

confidence: 99%

HLA-DPPolymorphisms Affect the Outcomes of Chronic Hepatitis B Virus Infections, Possibly through Interacting with Viral Mutations

Zhang

Yin

Zhang

et al. 2013

J Virol

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c Genetic polymorphisms of HLA-DP have been associated with hepatitis B virus (HBV) persistence. We aimed to determine the effect of HLA-DP polymorphisms on the generation of HBV mutations and their interactions on the outcomes of HBV infection. rs3077, rs3135021, rs9277535, and rs2281388 were genotyped in 1,342 healthy controls, 327 HBV clearance subjects, and 2,736 HBV-positive subjects, including 1,108 hepatocellular carcinoma (HCC) patients, using quantitative PCR. HBV mutations were determined by sequencing. Multiplicative interactions of HLA-DP polymorphisms and viral mutations were assessed by multivariate logistic regression. rs3077 (from subjects with genotype CT combined with those from subjects with genotype TT [CT؉TT] versus CC), rs3135021 (GA؉AA versus GG), rs9277535 (GA؉AA versus GG), and rs2281388 (CC versus CT؉TT) significantly decreased HBV persistence. This effect was found only in genotype B HBV-infected subjects compared to HBV clearance subjects. HLA-DP polymorphisms promoting HBV clearance were associated with a lower prevalence of mutations increasing HCC risk (C1653T, T1674C/G, A1846T, G1896A and pre-S2 mutations and pre-S deletion in genotype C) and a higher prevalence of mutations decreasing HCC risk (G1652A, T1673C, T1674C, G1719T, G1730C, and G1799C in genotype B and A1727T in genotype C). Significant effects of viral mutations on cirrhosis and HCC were selectively evident in those with HLA-DP polymorphisms promoting HBV persistence. The interactions of C1653T, T1674C/G, and G1896A mutations with HLA-DP polymorphisms promoting HBV clearance significantly decreased cirrhosis risk. The interaction of rs9277535 AA with the T1674C/G or G1719T mutation in genotype C significantly decreased HCC risk. In conclusion, HLA-DP polymorphisms affect genotype B HBV clearance, regulate immune selection of viral mutations, and influence cirrhosis and HCC risks contributed by HBV mutations. Chronic infection with hepatitis B virus (HBV) currently affects 350 million to 400 million people worldwide, and over 200,000 and 300,000 HBV-infected subjects die from decompensated hepatic cirrhosis (HC) and hepatocellular carcinoma (HCC), respectively, each year (1, 2). Chronic HBV infection results in approximately one-third of all HC cases and more than one-half of all HCC cases worldwide (3). The World Health Organization includes HBV in "group 1" human carcinogens (4). According to a sequence divergence of Ͼ8% in the entire genome, HBV has been classified into at least 8 genotypes so far. HBV genotypes have distinct geographic distributions and have been shown to differ with regard to clinical liver diseases, outcomes, and responses to interferon treatment (5). In East Asia, where HBV genotypes B and C are endemic, viral factors of HBV, including genotype C infection, hepatitis B virus e antigen (HBeAg) expression, high viral load (Ͼ10 4 copies/ml), and mutations in the enhancer II/basal core promoter/precore (EnhII/BCP/PC) and the pre-S regions, as well as active hepatic inflammation contribute greatly to ...

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Cytotoxic T lymphocyte responses and CTL epitope escape mutation in HBsAg, anti-HBe positive individuals

Cited by 23 publications

References 38 publications

Influence of HLA Alleles on Shedding of Kaposi Sarcoma–Associated Herpesvirus in Saliva in an African Population

Influence of HLA Alleles on Shedding of Kaposi Sarcoma–Associated Herpesvirus in Saliva in an African Population

Comparison Study on the Complete Sequence of Hepatitis B Virus Identifies New Mutations in Core Gene Associated with Hepatocellular Carcinoma

HLA-DPPolymorphisms Affect the Outcomes of Chronic Hepatitis B Virus Infections, Possibly through Interacting with Viral Mutations

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