Association of Pre-S/S and Polymerase Mutations with Acute and Chronic Hepatitis B Virus Infections in Patients from Rio de Janeiro, Brazil

Viruses. 2022 Jun 24;14(7):1375. doi: 10.3390/v14071375.

Abstract

Several hepatitis B virus (HBV)-related factors, including the viral load, genotype, and genomic mutations, have been linked to the development of liver diseases. Therefore, in this study we aimed to investigate the influence of HBV genetic variability during acute and chronic infection phases. A real-time nested PCR was used to detect HBV DNA in all samples (acute, n = 22; chronic, n = 49). All samples were sequenced for phylogenetic and mutation analyses. Genotype A, sub-genotype A1, was the most common genotype in the study population. A total of 190 mutations were found in the pre-S/S gene area and the acute profile revealed a greater number of nucleotide mutations (p < 0.05). However, both profiles contained nucleotide mutations linked to immune escape and an increased risk of hepatocellular carcinomas (acute, A7T; chronic, A7Q). Furthermore, 17 amino acid substitutions were identified in the viral polymerase region, including the drug resistance mutations lamivudine and entecavir (rtL180M), with statistically significant differences between the mutant and wild type strains. Owing to the natural occurrence of these mutations, it is important to screen for resistance mutations before beginning therapy.

Keywords: acute; chronic; hepatitis B infection; mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brazil / epidemiology
  • DNA, Viral / genetics
  • Drug Resistance, Viral / genetics
  • Genotype
  • Hepatitis B virus / genetics
  • Hepatitis B*
  • Hepatitis B, Chronic*
  • Humans
  • Lamivudine / therapeutic use
  • Mutation
  • Nucleotides
  • Phylogeny
  • Protein S / genetics*

Substances

  • DNA, Viral
  • Nucleotides
  • Protein S
  • Lamivudine

Grants and funding

This study was financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil (CAPES), Finance Code 001; the Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ); and the Oswaldo Cruz Institute, who approved the project and funded the research with scholarships and grants.