Higher detection rates of amino acid substitutions in HBV reverse transcriptase/surface protein overlapping sequence is correlated with lower serum HBV DNA and HBsAg levels in HBeAg-positive chronic hepatitis B patients with subgenotype B2

Su, Mingze; Xiang, Kuanhui; Li, Yao; Li, Yutang; Deng, Juan; Xu, Xizhan; Yan, Lei; Zhang, Hui; Li, Tong

doi:10.1016/j.meegid.2016.03.019

Cited by 19 publications

(22 citation statements)

References 30 publications

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“…We selected only genotype C HBeAg-positive patients to exclude the potential impacts of HBV genotype, HBeAg status and disease progression on sequence mutation analysis. In addition, genotype C HBV is the most prevalent genotype in China and some areas of Asia [16, 10, 9, 17]. …”

Section: Methodsmentioning

confidence: 99%

“…However, significantly different serum HBsAg levels could be found in CHB patients with the same disease progression, HBV genotype and HBeAg status [9]. Locarnini et al .…”

Section: Introductionmentioning

confidence: 99%

“…Locarnini et al . showed that serum HBsAg levels only correlated with HBV DNA loads during the immune clearance phase for patients with HBV genotype B and C infection [10, 9]. A better understanding of the mechanisms behind serum HBsAg level fluctuation is of clinical importance.…”

Section: Introductionmentioning

confidence: 99%

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Effects of amino acid substitutions in hepatitis B virus surface protein on virion secretion, antigenicity, HBsAg and viral DNA

Xiang

Michailidis

Ding

et al. 2017

Journal of Hepatology

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Background & Aims As important virological markers, serum HBsAg and HBV DNA levels show large fluctuations among chronic hepatitis B (CHB) patients. The aim of this study was to reveal the potential impact and mechanisms of amino acid (AA) substitutions in small hepatitis B surface proteins (SHBs) on serum HBsAg and HBV DNA levels. Methods Serum samples from 230 untreated chronic hepatitis B patients with genotype C HBV were analyzed in terms of HBV DNA levels, serological markers of HBV infection and SHBs sequences. In vitro functional analysis of the identified SHBs mutants was performed. Results Among 230 SHBs sequences, there were 39 (16.96%) sequences with no mutation detected (wild-type, WT) and 191 (83.04%) with single or multiple mutations. SHBs consist of 226 AAs, of which 104 (46.02%) had mutations in our study. Some mutations (e.g. sE2G, sL21R, sG24K, sT47A/K, sC69stop (sC69*), sL95W, sL98V, and sG145R) negatively correlated with serum HBsAg levels. HBsAg and HBV DNA levels from this group of patients had a positive correlation (r = 0.61, p < 0.001). In vitro analysis showed that these mutations reduced extracellular HBsAg and HBV DNA levels by restricting virion secretion and antibody binding capacity. Virion secretion could be rescued for sE2G, sC69*, and sG145R by co-expression of WT HBsAg. Conclusion The serum HBsAg levels were lower in untreated CHB patients with novel SHBs mutations outside the major antigenic region than those without mutations. Underlying mechanisms include impairment of virion secretion and lower binding affinity to antibodies used for HBsAg measurements.

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Section: Methodsmentioning

confidence: 99%

“…However, significantly different serum HBsAg levels could be found in CHB patients with the same disease progression, HBV genotype and HBeAg status [9]. Locarnini et al .…”

Section: Introductionmentioning

confidence: 99%

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Effects of amino acid substitutions in hepatitis B virus surface protein on virion secretion, antigenicity, HBsAg and viral DNA

Xiang

Michailidis

Ding

et al. 2017

Journal of Hepatology

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“…The current study aimed at analyzing serum HBV RNA in 483 patients with untreated HBeAg-positive andnegative CHB genotype B or C infection, the most prevalent HBV genotypes in China and Asia (12,13). The study also aimed at finding the potential factors affecting the levels of serum HBV RNA and revealing how it is correlated with the other viral factors, such as serum HBV DNA and HBsAg.…”

Section: Objectivesmentioning

confidence: 99%

“…The quantification of serum HBsAg was carried out by ARCHITECT HBsAg kit (Abbott Diagnostics) with a detection range of 0.05 -250 IU/mL. The HBV subgenotyping by reverse transcriptase (RT) sequencing was performed following the standard operating procedure of the laboratory as described in authors' previous reports (12,15). The phylogenetic trees construction and nucleotide divergence analyses with clinically isolated and reference sequences for known subgenotypes were carried out by MEGA 7.0 software using neighborjoining method and Kimura 2-parameter algorithm with bootstrapping 1000 replicates.…”

Section: Serological Tests For Hbv Markermentioning

confidence: 99%

Characterization of Serum HBV RNA in Patients with Untreated HBeAg-Positive and -Negative Chronic Hepatitis B Infection

et al. 2018

Hepat Mon

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Background: The serum hepatitis B virus (HBV) RNA is suggested as a potential new biomarker of HBV infection. However, it is not fully understood. Objectives: The current study aimed at characterizing serum HBV RNA in patients with untreated chronic hepatitis B (CHB) and genotype B and C HBV infection. Methods: A large cohort of 483 patients with hepatitis B e antigen (HBeAg)-positive and -negative was performed. The routine serum biomarkers of HBV infection were tested. HBV genotyping was carried out by direct sequencing. Serum HBV RNA levels were quantified using a method described in the authors' previous study (lower limit of detection: 66.7 IU/mL). Results: Serum HBV RNA was detected in 92.5% (394/426) of the patients with HBeAg-positive and 31.6% (18/57) of HBeAg-negative ones; a positive association was observed between HBeAg and HBV RNA statuses in the subjects. Alanine aminotransferase (ALT), HBV DNA, and genotype were the independent predictors in patients with HBeAg-positive CHB (P = 0.024, 0.001 and 0.014, respectively), while it was HBV DNA in the negative ones (P = 0.000) for serum HBV RNA detectability. Serum HBV RNA was positively correlated with ALT, aspartate transaminase (AST) and HBV DNA, regardless of HBeAg status, and with hepatitis B surface antigen (HBsAg) in HBeAg-positive ones (P < 0.05). Conclusions: Serum HBV RNA may be affected by HBeAg status, serum HBV DNA, HBsAg levels, HBV genotype, ALT, and AST levels. There might be some similarities between the characteristics of serum HBV RNA, and serum HBV DNA and HBsAg, regardless of its distinctive features. The roles of serum HBV RNA in viral replication, infection, survival, disease progression, and antiviral responses need to be investigated in further studied.

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Analysis of HBsAg mutations in the 25 years after the implementation of the hepatitis B vaccination plan in China

Teng

Lin

et al. 2020

Virus Genes

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Higher detection rates of amino acid substitutions in HBV reverse transcriptase/surface protein overlapping sequence is correlated with lower serum HBV DNA and HBsAg levels in HBeAg-positive chronic hepatitis B patients with subgenotype B2

Cited by 19 publications

References 30 publications

Effects of amino acid substitutions in hepatitis B virus surface protein on virion secretion, antigenicity, HBsAg and viral DNA

Effects of amino acid substitutions in hepatitis B virus surface protein on virion secretion, antigenicity, HBsAg and viral DNA

Characterization of Serum HBV RNA in Patients with Untreated HBeAg-Positive and -Negative Chronic Hepatitis B Infection

Analysis of HBsAg mutations in the 25 years after the implementation of the hepatitis B vaccination plan in China

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