HBV Core Region Variability: Effect of Antiviral Treatments on Main Epitopic Regions

Homs, María; Jardí, Rosendo; Buti, Marı́a; Schaper, Melanie; Tabernero, David; Fernández-Fernández, Pilar; Quer, Josep; Esteban, Rafael; Rodríguez‐Frías, Francisco

doi:10.3851/imp1701

Cited by 13 publications

(5 citation statements)

References 43 publications

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“…In contrast, preCore MfAA was not significantly different between any of the groups, which could indicate that the host immune response mainly acts against Core epitopes in patients with fluctuating HBeAg. In fact, preCore variants and positive selection of Core variants were common in HBeAg-negative and fluctuating patients, in keeping with results from our previous studies [8], [22]. These findings may result from HBV adaptation under host immune pressure, or even be due to an effect of antiviral treatment on the Core gene.…”

Section: Discussionsupporting

confidence: 90%

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Clinical Application of Estimating Hepatitis B Virus Quasispecies Complexity by Massive Sequencing: Correlation between Natural Evolution and On-Treatment Evolution

et al. 2014

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AimTo evaluate HBV quasispecies (QA) complexity in the preCore/Core regions in relation to HBeAg status, and explore QA changes under natural evolution and nucleoside analogue (NUC) treatment.MethodsUltra-deep pyrosequencing of HBV preCore/Core regions in 30 sequential samples (baseline [diagnosis], treatment-free, and treatment-nonresponse) from 10 retrospectively selected patients grouped according to HBeAg status over time: HBeAg+ (N = 4), HBeAg- (N = 2), and fluctuating HBeAg (transient seroreversion/seroconversion pattern) (N = 4). QA complexity was defined by Shannon entropy, mutation frequency, nucleotide diversity, and mutation frequency of amino acids (MfAA) in preCore and Core.ResultsThe QA was less complex in HBeAg+ than in HBeAg- or fluctuating HBeAg. High complexity in preCore was associated with decreased viral replication (preCore MfAA negatively correlated with HBV-DNA, p = 0.005). QA complexity in the treatment-free period negatively correlated with values seen during treatment. Specific variants were mainly selected in the Core region in HBeAg- and fluctuating HBeAg patients, suggesting higher immune pressure than in HBeAg+.ConclusionsThe negative correlation between QA natural evolution and on-treatment evolution indicates the importance of pre-treatment QA study to predict QA changes in NUC nonresponders. Study of QA complexity could be useful for managing HBV infection.

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Section: Discussionsupporting

confidence: 90%

“…The region analyzed by UDPS, clustered positions 1757 to 2152 [16], covered the complete preCore (1814–1900) and the first 84 codons of the Core gene (1901–2152), which include the two main immunodominant epitopes flanked by amino acids 50 to 69 (Th 50–69) and by amino acids 74 to 84 (B74–84) [22].…”

Section: Methodsmentioning

confidence: 99%

Clinical Application of Estimating Hepatitis B Virus Quasispecies Complexity by Massive Sequencing: Correlation between Natural Evolution and On-Treatment Evolution

et al. 2014

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“…These mutations in the BCP region are caused by deletions or insertions in the C-terminal leading to severe clinical outcomes in chronic participants. Previously, a study of HBV core variability among HAART participants, as in our study, suggested that the presence of the T67N mutation significantly reduced T-cell proliferation in vitro when it occurred with mutation E64D [59]. In our study, these mutations occurred both in combination and independent of each other.…”

Section: Discussionsupporting

confidence: 75%

Prevalence of Hepatitis B Virus Mutations Associated with Hepatocellular Carcinoma in HBV and HIV Co-infected Adults in Botswana

Anderson¹,

Choga²,

Phinius³

et al. 2022

Preprint

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Mutations within the hepatitis B virus (HBV) genome have been associated with rapid progres-sion to hepatocellular carcinoma (HCC); however, there is limited information regarding the prevalence and impact of these mutations in most of sub-Saharan Africa, including Botswana. We aimed to determine the prevalence of HBV mutations known to be associated with progression to HCC using a retrospective, cross-sectional analysis of 48 previously generated HBV sequences from adults with concomitant HBV/HIV initiating HIV antiretroviral therapy in Botswana. The sequences were aligned with reference sequences, and HCC-associated mutations were manually identified using BioEdit. Sixteen (33.3 %) of 48 participant samples had 20 HCC-associated mu-tations. Seven HCC mutations were present in the core region, 4 in the preCore region, 7 in the X region, and one mutation in the surface region, as well as deletions within the preSurface 1 region. Seven of the 16 participants (43.8%) had multiple HCC-associated mutations. There were also previously uncharacterized mutations at positions with known HCC-associated mutations. HCC-associated mutations were common in this cohort; hence, some participants may require close clinical monitoring as they might be more prone to rapid disease progression. Other functionally uncharacterized polymorphisms were also detected and require characterization in future studies.

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“…In this study, the HBcAg mutations E64D, E77Q, A80I/T/V, and L116I were significantly associated with cirrhosis and HCC. Previously, a study of HBV core variability under antiviral therapy reported the presence of the E64D mutation during the course of HBV infection, and stated that this substitution significantly reduced T-cell proliferation in vitro when it occurred with mutation T67N (Homs et al, 2011 ). Similarly, the mutations associated with severe liver disease were reportedly concentrated in the center of HBcAg, in a region including amino acids 59–66 (Akarca and Lok, 1995 ).…”

Section: Discussionmentioning

confidence: 99%

The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease

Al‐Qahtani

Al-Anazi

Nazir

et al. 2018

Front. Cell. Infect. Microbiol.

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Viral mutations acquired during the course of chronic hepatitis B virus (HBV) infection are known to be associated with the progression and severity of HBV-related liver disease. This study of HBV-infected Saudi Arabian patients aimed to identify amino acid substitutions within the precore/core (preC/C) region of HBV, and investigate their impact on disease progression toward hepatocellular carcinoma (HCC). Patients were categorized according to the severity of their disease, and were divided into the following groups: inactive HBV carriers, active HBV carriers, liver cirrhosis patients, and HCC patients. Two precore mutations, W28* and G29D, and six core mutations, F24Y, E64D, E77Q, A80I/T/V, L116I, and E180A were significantly associated with the development of cirrhosis and HCC. Six of the seven significant core mutations that were identified in this study were located within immuno-active epitopes; E77Q, A80I/T/V, and L116I were located within B-cell epitopes, and F24Y, E64D, and V91S/T were located within T-cell epitopes. Multivariate risk analysis confirmed that the core mutations A80V and L116I were both independent predictors of HBV-associated liver disease progression. In conclusion, our data show that mutations within the preC/C region, particularly within the immuno-active epitopes, may contribute to the severity of liver disease in patients with chronic hepatitis. Furthermore, we have identified several distinct preC/C mutations within the study population that affect the clinical manifestation and progression of HBV-related disease. The specific identity of HBV mutations that are associated with severe disease varies between different ethnic populations, and so the specific preC/C mutations identified here will be useful for predicting clinical outcomes and identifying the HBV-infected patients within the Saudi population that are at high risk of developing HCC.

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HBV Core Region Variability: Effect of Antiviral Treatments on Main Epitopic Regions

Cited by 13 publications

References 43 publications

Clinical Application of Estimating Hepatitis B Virus Quasispecies Complexity by Massive Sequencing: Correlation between Natural Evolution and On-Treatment Evolution

Clinical Application of Estimating Hepatitis B Virus Quasispecies Complexity by Massive Sequencing: Correlation between Natural Evolution and On-Treatment Evolution

Prevalence of Hepatitis B Virus Mutations Associated with Hepatocellular Carcinoma in HBV and HIV Co-infected Adults in Botswana

The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease

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