HBsAg Variants: Common Escape Issues

Dindoost, Payam; Jazayeri, Seyed Mohammad; Karimzadeh, Hadi; Saberfar, Esmaeil; Miri, Seyyed Mohammad; Alavian, Seyed Moayed

doi:10.5812/jjm.4243

Cited by 15 publications

(10 citation statements)

References 90 publications

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“…The pattern of mutated distribution was established using the published data on the different HBV surface protein immune epitopes [19]. In total, 1, 4 and 4 regions have been proposed for B-cell, T-helper and CTL immune epitopes across the surface protein, respectively.…”

Section: Resultsmentioning

confidence: 99%

Naturally Occurring Surface Antigen Variants of Hepatitis B Virus in Tunisian Patients

Chaouch¹,

Taffon²,

Villano³

et al. 2016

Intervirology

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In Tunisia, the prevalence of naturally occurring surface (S) gene variants of hepatitis B virus (HBV) has not been determined. In the present study, the prevalence of these variants was examined in terms of the clinical and viral state in a series of 99 Tunisian patients with HBV infection. The S genes were amplified and directly sequenced. Genotype D was predominant (98%), 40.4% isolates belonged to subgenotypes D7 and 1 to subgenotype D2. The most common subtype was ayw2 (95.9%). In total, 60.6% of the studied strains harbored S mutations. Several novel mutation patterns were detected. Interestingly, the presence of S mutations was significantly correlated with the D7 subgenotype, low HBV DNA and advancing age (≥35 years), and tended to be higher in liver cirrhosis than in chronic infection. The global prevalence of the major hydrophilic region variants was 12.1%, with substitution S143L/T as the most frequent (4%). Only 33.9% of S substitutions produced amino acid changes in the polymerase gene. In conclusion, a high prevalence of naturally occurring HBsAg variants was observed among Tunisian HBV carriers. Natural viral variability in a geographical region and duration of infection are among the major factors associated with the occurrence of S mutations.

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Section: Resultsmentioning

confidence: 99%

Naturally Occurring Surface Antigen Variants of Hepatitis B Virus in Tunisian Patients

Chaouch¹,

Taffon²,

Villano³

et al. 2016

Intervirology

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“…A wide range of varaitions containing various amino acid substitutions across the 'a' determinant has been described in the literature (7,14,(16)(17)(18). Amino acid substitutions within the critical positions of structural proteins may influence their stability and structure and also effect their characteristics and interactions with other proteins.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that amino acid substitutions both outside and within the 'a' determinant of HBsAg could cause a reduced binding affinity to monoclonal antibodies developed against the 'a' determinant (14). To assess the antigenicity of the HBsAg mutants, all mutant sequences as well as wild HBsAg were subjected to the antibody epitope prediction server IEDB-AR (15).…”

Section: Evaluation Of Protein Antigenicitymentioning

confidence: 99%

Analysis of Antigenic and Conformational Changes in Hepatitis B Surface Antigen (HBsAg) Identified in Iranian Patients with Chronic Hepatitis B

et al. 2017

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Background: The 'a' determinant domain of hepatitis B surface antigen (HBsAg) (positions 124 to 147) is recognized by antibodies raised either naturally or induced by vaccine. Failure to protect against hepatitis B virus (HBV) infection may occur due to the conformational changes of 'a' determinant induced by mutations. Objectives: The present study analyzed the molecular and three-dimensional (3D) characteristics of the HBsAg 'a' determinant mutations among Iranian chronic hepatitis B (CHB) patients, who were vaccine and drug naive. Methods: Eighty patients with HBsAg positive test results were selected according to the data extracted from questionnaires. Serologic and molecular assays were performed using real-time Polymerase Chain Reaction (PCR) and subsequently surface nested PCR on CHB patients. Next, an extensive mutational analysis was applied following direct sequencing on HBsAg amplified genes. The potential impacts of altered antigenic and 3D properties of amino acid substitutions were carried out using bioinformatics approaches. Results: All patients were negative for HBeAg and positive for anti-HBe. Mutational analysis showed that 60 (75%) of 80 patients had at least one amino acid substitution. Several mutations were found in 'a' determinant (P127L, P127T, G130N, and S136Y). Bioinformatics investigations indicated that all mutations induced a conformational change in 'a' determinant region. P127L substitution led to a considerable decreased HBsAg antigenicity compared to other mutants. Conclusions: The current analyses revealed that the studied mutations induced a local change in the 'a' determinant conformation. These findings could be useful for the design of HBsAg detection assays, which may significantly improve the ability to detect particular HBsAg mutants.

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“…MHR proposed to have two major loops and one minor loop which defined by some disulphide bridge that join the epitope cluster for which majority of anti HBs directed are against the epitope between aa 107-137 or (138), 139-147 or(149) and 121-124 [28].…”

Section: Hepatitis B Surface Antigen (Hbsag)mentioning

confidence: 99%