Abstract

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.

Highlights

  • Hepatitis B virus (HBV) infection is a serious global health problem, which can cause a series of liver diseases (including chronic hepatitis B (CHB), cirrhosis, hepatic failure, and hepato-cellular carcinoma (HCC))[1]

  • Six males were in the experimental group while 3 females and 3 males were in the control group

  • The hepatitis B virus (HBV)-DNA levels in the experimental group were significantly lower than in the control group (6.57 ± 0.59 vs 7.57 ± 0.84 log10IU/ml, HBV DNA level >103, p = 0.038, Table 1), which is consistent with a previous study[27]

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Summary

Introduction

Hepatitis B virus (HBV) infection is a serious global health problem, which can cause a series of liver diseases (including chronic hepatitis B (CHB), cirrhosis, hepatic failure, and hepato-cellular carcinoma (HCC))[1]. According to the World Health Organization, more than 2 billion people worldwide have been exposed to HBV2, with an annual death toll of 650,000 from the associated diseases[3] It is well-known in the medical field that antibodies to hepatitis B surface antigen (HBsAg), anti-HBs, are capable of neutralizing HBsAg and clearance of HBV, which is characterized by the emergence of anti-HBs and the disappearance of HBsAg from peripheral blood[4]. 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, 22,23,24]. It is unreasonable to research coexistence of HBsAg and anti-HBs antibodies from the perspective of a partial HBV genome

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