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Updated: Oct 1, 2025
Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
Published on: November 7, 2018
Intra-host analysis of hepaciviral glycoprotein evolution reveals signatures associated with viral persistence and
André Gömer1, Richard J P Brown2, Stephanie Pfaender1
1Department for Molecular and Medical Virology, Ruhr University Bochum, Universitätsstr. 150, Bochum 44801, Germany.
Insights
No hepatitis C virus (HCV) vaccine exists due to high mutation rates and lack of animal models. Equine hepacivirus (EqHV) in horses may serve as a useful model to study HCV immune evasion strategies.
Area of Science:
- Virology
- Immunology
- Comparative Genomics
Background:
- Hepatitis C virus (HCV) remains a significant global health challenge with no available vaccine after 30 years.
- High HCV mutation rates and the lack of an immunocompetent animal model hinder vaccine development.
- Equine hepacivirus (EqHV), the closest known relative to HCV, offers a potential avenue for research.
Purpose of the Study:
- To investigate the intra-host viral population and evolutionary patterns of equine hepacivirus (EqHV) E1E2 glycoproteins.
- To compare EqHV evolution in horses with Hepatitis C virus (HCV) evolution in humans.
- To assess the potential of EqHV as a surrogate animal model for understanding HCV immune evasion.
Main Methods:
- Longitudinal sampling of sera from naturally and experimentally EqHV-infected horses and HCV-infected patients.
- Deep-sequencing of amplicon-based genomic regions encoding E1 and E2 surface glycoproteins.
- Comparative analysis of substitutional evolution patterns and selection pressures between EqHV and HCV populations.
Main Results:
- Intra-host viral diversity was higher in chronically infected horses and HCV patients compared to acutely infected horses.
- Hepatitis C virus (HCV) exhibited higher overall glycoprotein variability and stronger selection pressure, particularly in the E2 N-terminal region (HVR1).
- The hypervariable region 1 (HVR1) was identified as a unique characteristic of HCV, absent in hepaciviruses from non-human species.
Conclusions:
- Equine hepacivirus (EqHV) infection in horses demonstrates distinct evolutionary patterns compared to HCV.
- The absence of HVR1 in EqHV suggests its role in HCV's immune evasion strategy.
- Equine hepacivirus (EqHV) infection in horses represents a promising surrogate model for studying hepaciviral evolution and HCV's HVR1-mediated immune evasion.
Abstract:
Even 30 years after the discovery of the hepatitis C virus (HCV) in humans there is still no vaccine available. Reasons for this include the high mutation rate of HCV, which allows the virus to escape immune recognition and the absence of an immunocompetent animal model for vaccine development. Phylogenetically distinct hepaciviruses (genus Hepacivirus, family Flaviviridae) have been isolated from diverse species, each with a narrow host range: the equine hepacivirus (EqHV) is the closest known relative of HCV. In this study, we used amplicon-based deep-sequencing to investigate the viral intra-host population composition of the genomic regions encoding the surface glycoproteins E1 and E2. Patterns of E1E2 substitutional evolution were compared in longitudinally sampled EqHV-positive sera of naturally and experimentally infected horses and HCV-positive patients. Intra-host virus diversity was higher in chronically than in acutely infected horses, a pattern which was similar in the HCV-infected patients. However, overall glycoprotein variability was higher in HCV compared to EqHV. Additionally, selection pressure in HCV populations was higher, especially within the N-terminal region of E2, corresponding to the hypervariable region 1 (HVR1) in HCV. An alignment of glycoprotein sequences from diverse hepaciviruses identified the HVR1 as a unique characteristic of HCV: hepaciviruses from non-human species lack this region. Together, these data indicate that EqHV infection of horses could represent a powerful surrogate animal model to gain insights into hepaciviral evolution and HCVs HVR1-mediated immune evasion strategy.
