Deep sequencing identifies hepatitis B virus core protein signatures in chronic hepatitis B patients

Meike H van der Ree1, Louis Jansen1, Matthijs R A Welkers2

  • 1Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands; Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.

Antiviral Research
|August 20, 2018
PubMed

Insights

Amino acid differences in hepatitis B core antigen (HBc) were identified between chronic hepatitis B (CHB) patient subgroups. These variations correlate with HBeAg status and treatment response, offering insights into disease progression.

Area of Science:

  • Virology
  • Immunology
  • Genetics

Background:

  • Chronic hepatitis B (CHB) is a significant global health concern.
  • Understanding viral protein variations is crucial for managing CHB.
  • Hepatitis B e antigen (HBeAg) status and treatment response are key clinical indicators in CHB.

Purpose of the Study:

  • To identify amino acid differences in the hepatitis B core antigen (HBc) between CHB patient subgroups.
  • To correlate HBc amino acid variations with HBeAg serostatus.
  • To investigate the association between HBc amino acid changes and response to combination antiviral therapy.

Main Methods:

  • Deep sequencing of the HBc gene was performed on samples from 89 CHB patients.
  • Sequence Harmony software was utilized for comparative amino acid analysis.
  • Patients were stratified based on HBeAg positivity/negativity and response to peginterferon/adefovir therapy.

Main Results:

  • Significant differences in amino acid frequencies at 54 HBc positions were found between HBeAg-positive and -negative patients.
  • Twenty-two HBc positions showed differential amino acid usage between treatment responders and non-responders in HBeAg-negative patients.
  • A higher proportion of non-consensus sequences at specific HBc sites was observed in HBeAg-negative patients, negatively correlating with HBV DNA and HBsAg levels.

Conclusions:

  • Sequence Harmony effectively identified amino acid alterations in HBc linked to HBeAg status.
  • Specific HBc amino acid changes are associated with treatment outcomes in CHB patients receiving combination therapy.
  • These findings contribute to a deeper understanding of HBc protein's role in CHB pathogenesis and treatment response.
Abstract

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