Mutations in the S gene and in the overlapping reverse transcriptase region in chronic hepatitis B Chinese patients with coexistence of HBsAg and anti-HBs

Ding, Feng; Miao, Xili; Li, Yanxia; Dai, Jun; Yu, Honggang

doi:10.1016/j.bjid.2015.08.014

Cited by 18 publications

(26 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%

“…Usually, positive anti‐HBs status means that HBV has been cleared, and patient has gained immunity. However, the traditional opinion has been challenged by the discovery of co‐existence of HBsAg and anti‐HBs in chronic HBV infections . The concurrent status of HBsAg and anti‐HBs been explained for decades, but the mechanism remains largely unknown and controversial .…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

confidence: 99%

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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“…Moreover, it is essential to note that 8% of patients had mutations in the ‘a' determinant of the MHR. Higher mutation frequencies of MHR variants (60%) were observed inside the ‘a' determinant, which confirm the finding of previous studies [27,39,40]. …”

Section: Discussionsupporting

confidence: 91%

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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“…In addition, because of amplification and sequencing problems, previous studies that compared HBV mutants between patients with the coexistence of HBsAg and anti-HBs antibodies and controls (patients who were HBsAg positive but anti-HBs negative) focused only on individual parts of the genome (preS, HBsAg and RT) which is associated with viral replication and immunoreaction 12, 22–24 . However, the viability and function of viruses are the result of interplay between all genes.…”

Section: Introductionmentioning

confidence: 99%

Evolution of full-length genomes of HBV quasispecies in sera of patients with a coexistence of HBsAg and anti-HBs antibodies

Zhou¹,

Li²,

Li³

et al. 2017

Sci Rep

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Although the evolutionary changes of viral quasispecies are correlated to the pathological status of a disease, little is known in the coexistence of hepatitis B surface antigen (HBsAg) and antibodies to these antigens (anti-HBs). To examine evolutionary changes in hepatitis B virus (HBV) and their relationship to the coexistence of HBsAg and anti-HBs antibodies, HBV genomes in patients with a coexistence of HBsAg and anti-HBs antibodies (experimental group) and HBsAg positive without anti-HBs (control group) were assessed. Our results showed that quasispecies diversity was significantly higher in the experimental group for large HBsAg (LHBsAg), middle HBsAg (MHBsAg), and HBsAg genes. LHBsAg harbored dN/dS values eight times higher in the experimental group; however, the mean dN/dS ratios in genes HbxAg, Pol and PreC/C of the experimental patients had an opposite trend. Phylogenetic trees in the experimental group were more complex than the control group. More positive selection sites, mutations and deletions were observed in the experimental group in specific regions. Furthermore, several amino acid variants in epitopes were potentially associated with the immune evasion. In conclusion, cumulative evolutionary changes in HBV genome that facilitate immune evasion provide insights into the genetic mechanism of a coexistence of HBsAg and anti-HBs antibodies.

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Mutations in the S gene and in the overlapping reverse transcriptase region in chronic hepatitis B Chinese patients with coexistence of HBsAg and anti-HBs

Abstract: In chronic patients, the concurrent HBsAg/anti-HBs serological profile is associated with an increased aa variability in several key areas of HBV genome. Additional research on these genetic mutants are needed to clarify their biological significance for viral persistence.

Cited by 18 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

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

Evolution of full-length genomes of HBV quasispecies in sera of patients with a coexistence of HBsAg and anti-HBs antibodies

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