Amino acid similarities and divergences in the small surface proteins of genotype C hepatitis B viruses between nucleos(t)ide analogue-naïve and lamivudine-treated patients with chronic hepatitis B

Ding, Hai; Liu, Baoming; Zhao, Chengyu; Yang, Jingxian; Yan, Chunhui; Yan, Lei; Zhang, Hui; Li, Tong

doi:10.1016/j.antiviral.2013.11.015

Cited by 23 publications

(16 citation statements)

References 29 publications

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“…), sC69* (8.69% vs 4.17%, P > 0.05) and sW182* (8.69% vs 4.17%, P > 0.05). As reported previously, these mutations results in rtS78T and rtV191I mutations in RT region, respectively. Moreover, four inserted mutations were found in group I, which may lead to the change of HBsAg's antigenicity.…”

Section: Resultssupporting

confidence: 76%

Mutation in the S gene of hepatitis B virus and anti‐HBs subtype‐nonspecificity contributed to the co‐existence of HBsAg and anti‐HBs in patients with chronic hepatitis B virus infection

Chen

et al. 2017

Journal of Medical Virology

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The mechanism for the co-existence of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) in chronic HBV infected patients remains controversial. This study aimed to explore the role of HBV S gene mutation and anti-HBs subtype-nonspecificity in patients with simultaneous HBsAg/anti-HBs positivity. Chronic HBV infections with (n = 145, group I) and without (n = 141, group II) anti-HBs were included. The S gene was amplified and sequenced. The neutralization experiment was used in group I patients' sera to determine the specificity of anti-HBs. Additionally, the HBV vaccinated persons' sera were used to estimate the neutralize capacity of anti-HBs against HBsAg in group I patients. Results showed that 2.63% (145/5513) chronic HBV infected patients had positive results for anti-HBs. HBsAg amino acid (aa) substitution rate in 35 patients of group I was significantly higher than that in 58 patients of group II (1.89% vs 0.95%, P < 0.05), especially within "a" determinant (4.05% vs 1.22%, P < 0.05). In group I patients, anti-HBs in (74.29%, 26/35) patients was not directed to the subtypes of the co-existing HBsAg. Besides, some HBsAg variations in group I patients, sG145R mutation, inserted mutations, and continuous aa mutations within the major hydrophilic region (MHR), decreased the neutralized capacity of anti-HBs from HBV vaccinated persons. In conclusion, both of HBsAg mutation and anti-HBs subtype-nonspecificity contributed to the co-existence of HBsAg and anti-HBs in chronic HBV infection. HBV vaccine recipients may still have a risk of HBV infection when exposure to patients with simultaneous HBsAg/anti-HBs positivity.

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Section: Resultssupporting

confidence: 76%

Mutation in the S gene of hepatitis B virus and anti‐HBs subtype‐nonspecificity contributed to the co‐existence of HBsAg and anti‐HBs in patients with chronic hepatitis B virus infection

Chen

et al. 2017

Journal of Medical Virology

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“…In this study, we used the Chinese HBV genotype B and C reference strains, as they provide the most appropriate reference sequences to which the OBI and control group sequences are compared. At least partially due to this reason, the amino acid substitution rate in the S protein in our study was significantly lower than that reported by previous studies [Lada et al, ; Yuan et al, ; Shahmoradi et al, ; Ding et al, ]. Besides, most of those studies chose HBeAg‐positive patients with chronic HBV infection as the control group when analyzing the gene mutations in OBI.…”

Section: Discussioncontrasting

confidence: 67%

Occult hepatitis B virus infection among people with a family history of chronic hepatitis B virus infection

Zhang

Dai

et al. 2015

Journal of Medical Virology

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0/31, 0%). However, none of these differences was statistically significant (P = 0.237, 0.199, 0.201, respectively). In summary, the prevalence of OBI among HBsAg-negative people with a family history of chronic HBV infection was significantly higher than that in Chinese blood donors. However, S region mutations and the escape mechanism are not likely to be the major causes of increased prevalence of OBI.

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“…The sC69* also occurs in genotype D [32]. Several mutations including sC69*, sL95W and sL98V were also identified in 60 samples of HBeAg-negative CHB patients (Supplementary Table 5) [3]. Another limitation is that we focused on the S region of the HBV genome.…”

Section: Discussionmentioning

confidence: 99%

“…The hepatitis B surface antigen (HBsAg), a major viral protein secreted into patient serum, consists of three distinct, but structurally related proteins: the large, middle and small hepatitis B surface proteins (LHBs, MHBs, and SHBs, respectively). Within the SHBs, the amino acids (AA) 99 to 169 region is termed as the major hydrophilic region (MHR), where AAs 124–147 is defined as the ‘a’ determinant, a dominant neutralizing epitope [3]. Antibodies used in commercial detection kits usually recognize and bind to this region.…”

Section: Introductionmentioning

confidence: 99%

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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Amino acid similarities and divergences in the small surface proteins of genotype C hepatitis B viruses between nucleos(t)ide analogue-naïve and lamivudine-treated patients with chronic hepatitis B

Cited by 23 publications

References 29 publications

Mutation in the S gene of hepatitis B virus and anti‐HBs subtype‐nonspecificity contributed to the co‐existence of HBsAg and anti‐HBs in patients with chronic hepatitis B virus infection

Mutation in the S gene of hepatitis B virus and anti‐HBs subtype‐nonspecificity contributed to the co‐existence of HBsAg and anti‐HBs in patients with chronic hepatitis B virus infection

Occult hepatitis B virus infection among people with a family history of chronic hepatitis B virus infection

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

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