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Strong Replication Interference Between Hepatitis Delta Viruses in Human Liver Chimeric Mice.

Katja Giersch1, Lennart Hermanussen1, Tassilo Volz1

  • 1Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Frontiers in Microbiology
|July 26, 2021
PubMed
Summary

Hepatitis D Virus (HDV) genotypes can infect the same liver but rarely the same cell. Sequential infections show that the first-inoculated HDV strain dominates, impairing super-infection and hindering recombination.

Keywords:
HDVgenotypeshepatitis deltahuman liver chimeric micehumanized micein vivorecombinationreplication

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Area of Science:

  • Hepatology
  • Virology
  • Molecular Biology

Background:

  • Hepatitis D Virus (HDV) has eight genotypes with varying clinical outcomes.
  • Understanding inter-genotypic interactions and viral interference is crucial for HDV co-infection and recombinant development.

Purpose of the Study:

  • To investigate virological differences between HDV-1 and HDV-3.
  • To assess their capacity for co-infection and replication within the same host liver and hepatocytes in vivo.

Main Methods:

  • Human liver chimeric mice were infected with HBV and either HDV-1, HDV-3, or both simultaneously.
  • Sequential infections with different HDV genotypes and strains were performed.
  • Virological parameters were analyzed using qRT-PCR, RNA in situ hybridization, and immunofluorescence staining.

Main Results:

  • HDV-3 exhibited faster spreading and higher intrahepatic levels than HDV-1 during co-infection.
  • HDV-3 became the dominant genotype when both were introduced simultaneously.
  • While both genotypes were found in the same liver, they were rarely detected within the same hepatocyte.

Conclusions:

  • Co-infection with divergent HDV genotypes can occur in the same liver but not typically within the same cell.
  • Sequential super-infection was significantly impaired, suggesting virus interference mechanisms limit replication within a single cell.
  • These interference mechanisms may hinder the development of HDV inter-genotypic recombinants.