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Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle
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Monocyte Transcriptome in Different Phases of Chronic Hepatitis B Virus Infection Uncovers Potential Functional

Prakriti Sinha1, Vaishali Bhardwaj2, Abaranjitha Muniyasamy1

  • 1National Institute of Immunology, New Delhi, India.

Viral Immunology
|July 25, 2024
PubMed
Summary

Hepatitis B virus (HBV) infection involves distinct phases. Monocyte gene expression analysis reveals unique molecular signatures in each phase, impacting immune cell function and viral control.

Keywords:
CD14+biomarkershepatitis B virusimmunological phasesmonocytestranscriptome study

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Area of Science:

  • Immunology
  • Virology
  • Transcriptomics
  • Hepatitis B Virus (HBV) Infection

Background:

  • Chronic hepatitis B virus (HBV) infection progresses through immune-tolerant (IT), immune-clearance (IC), and inactive (IN) phases.
  • While adaptive immunity is key to viral control, the role of innate immune cells, like monocytes, is less understood.
  • Understanding monocyte involvement is crucial for deciphering HBV infection dynamics.

Purpose of the Study:

  • To investigate the monocyte transcriptome across different phases of chronic HBV infection.
  • To identify unique differentially expressed genes (DEGs) specific to each infection phase.
  • To elucidate the functional impact of these DEGs on monocyte behavior during HBV infection.

Main Methods:

  • Isolation of CD14+ peripheral blood monocytes from patients in IT, IC, IN phases and healthy controls.
  • RNA sequencing to analyze monocyte transcriptomes.
  • Bioinformatic analysis of DEGs and pathway modulation.
  • Quantitative reverse transcription PCR (qRT-PCR) for gene validation.
  • Receiver Operating Characteristic (ROC) curve analysis for diagnostic potential.

Main Results:

  • TNFRSF12A was upregulated across all HBV infection phases.
  • The IN phase showed unique upregulation of six genes, including PI3 and SPINK1.
  • E2F7 was consistently downregulated in the IT phase, while IL23A and PI3 were downregulated in the IC phase.
  • Monocyte function appeared suppressed in IT and IC phases, with some metabolic activity in the IN phase.

Conclusions:

  • Monocyte transcriptomic profiles differ significantly across HBV infection phases.
  • Specific genes are uniquely expressed in each phase, offering potential biomarkers for HBV progression.
  • Monocyte functional states vary across phases, with suppression in early stages and partial recovery in the inactive phase.