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Conservation and variability of hepatitis B core at different chronic hepatitis stages

Marçal Yll1, Maria Francesca Cortese1, Mercedes Guerrero-Murillo2

  • 1Liver Pathology Unit, Departments of Biochemistry and Microbiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona 08035, Spain.

World Journal of Gastroenterology
|June 12, 2020
PubMed

Insights

Researchers identified conserved regions in the hepatitis B virus (HBV) core gene (HBC) and protein. These regions, along with a specific P79Q substitution, may indicate disease progression and offer targets for new HBV therapies.

Area of Science:

  • Virology and Molecular Biology
  • Hepatitis B Virus (HBV) Pathogenesis
  • Genomic and Proteomic Analysis

Background:

  • Current hepatitis B virus (HBV) treatments cannot eradicate the infection, necessitating novel therapeutic strategies.
  • The HBV core protein, encoded by the HBV core gene (HBC), plays a crucial role in the HBV life cycle and is a potential target for new therapies.
  • Alterations in HBC protein sequence may serve as biomarkers for HBV disease progression.

Purpose of the Study:

  • To identify hyper-conserved regions within the HBV core gene (HBC) using next-generation sequencing.
  • To evaluate these conserved regions as potential prognostic factors for HBV infection.
  • To explore these regions as targets for novel therapeutic and diagnostic approaches against HBV.

Main Methods:

  • Next-generation sequencing (Illumina MiSeq) was employed to analyze the HBV core gene (HBC) region (nt 1863-2483) from 38 chronic HBV patients.
  • Patients were categorized into chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) groups.
  • Nucleotide and amino acid conservation patterns were analyzed using sliding window analysis, and sequence variations were compared across groups.

Main Results:

  • Three hyper-conserved nucleotide regions and two hyper-conserved amino acid regions in HBC were identified across all patient groups.
  • Differential conservation patterns were observed in specific nucleotide and amino acid regions between CHB, LC, and HCC groups.
  • A significant P79Q amino acid substitution was found predominantly in the HCC group, suggesting a potential link to disease progression.

Conclusions:

  • The identified differentially conserved HBC regions and the P79Q substitution are potentially associated with HBV disease progression.
  • These specific conserved regions represent promising targets for the development of future therapeutic and diagnostic strategies for HBV infection.
  • Next-generation sequencing effectively identified key genetic markers within the HBV core gene related to disease severity.
Abstract

Keywords:
Amino acid substitutionGene therapyGenetic conservationHepatitis B core geneHepatitis B virusNext-generation sequencingSmall interfering RNA

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