Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics

Amy Cross1, James M Harris2, Edward Arbe-Barnes3

  • 1Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.

Egastroenterology
|August 16, 2024
PubMed

Insights

Spatial transcriptomics reveals distinct intrahepatic pathways in chronic hepatitis B (CHB) with hepatitis delta virus (HDV) or HIV co-infection. This method aids understanding of complex liver disease and guides personalized treatments.

Area of Science:

  • Hepatology
  • Immunology
  • Genomics

Background:

  • Chronic hepatitis B (CHB) intrahepatic processes, particularly with hepatitis delta virus (HDV) or HIV co-infection, require deeper understanding.
  • Spatial transcriptomics offers novel insights into complex intrahepatic biology for personalized treatment strategies.

Purpose of the Study:

  • To evaluate spatial transcriptomics for characterizing the intrahepatic transcriptional landscape, cellular composition, and biological pathways in liver biopsies.
  • To investigate HBV, HDV, and HIV co-infections using this advanced methodology.

Main Methods:

  • Utilized NanoString GeoMx digital spatial profiling on FFPE liver biopsies from treatment-naïve patients.
  • Quantified gene expression using the GeoMx Human Whole Transcriptome Atlas and deconvoluted cell type proportions.
  • Applied weighted gene correlation network analysis to evaluate transcriptomic signatures.

Main Results:

  • Identified spatially discrete transcriptomic signatures and distinct biological pathways linked to HBV infection and immune responses.
  • Observed shared features like 'cytotoxicity' and 'B cell receptor signalling' across patients.
  • HDV/HBV co-infection showed upregulated apoptosis and immune cell recruitment genes; HIV/HBV co-infection revealed interferon response regulation genes. γδT cells were abundant in HDV/HBV samples. Hepatocyte function differences suggest metabolic disruption in HDV/HBV co-infection.

Conclusions:

  • This proof-of-principle study demonstrates the utility of spatial transcriptomics in dissecting complex intrahepatic immune landscapes.
  • The platform highlights relevant host pathways contributing to disease pathogenesis in viral hepatitis co-infections.
Abstract

Related Concept Videos

Viruses with RNA Genomes01:29

Viruses with RNA Genomes

RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
Hepatitis01:25

Hepatitis

Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver. The...
Viral Hepatitis I: Introduction01:28

Viral Hepatitis I: Introduction

Viral hepatitis is an inflammatory condition of the liver caused by infection with hepatotropic viruses, most commonly hepatitis A, B, C, D, and E. Despite variations in structure and transmission, all viruses mentioned infect hepatocytes and provoke immune responses that can hinder liver function. Additionally, some non-hepatotropic viruses can also lead to hepatic inflammation.Hepatitis A VirusHepatitis A virus (HAV) is transmitted through the fecal–oral route, typically by ingestion of food...