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A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
Proteoglycans act as cellular hepatitis delta virus attachment receptors
Oscar Lamas Longarela1, Tobias T Schmidt, Katrin Schöneweis
1Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Heidelberg, Baden-Württemberg, Germany.
Plos One
|March 19, 2013
Summary
Hepatitis delta virus (HDV) entry into liver cells requires heparan sulfate proteoglycans, not purinergic receptors. This finding clarifies HDV infection mechanisms for millions co-infected with hepatitis B virus (HBV).
Area of Science:
- Hepatology and Virology
- Molecular and Cellular Biology
Background:
- Hepatitis delta virus (HDV) co-infects over 15 million people worldwide with hepatitis B virus (HBV).
- Early steps of HBV/HDV entry, including cell attachment and receptor interactions, remain poorly understood.
- Heparan sulfate proteoglycans (HSPGs) are confirmed HBV attachment factors, while purinergic receptors (P2XRs) have been suggested as entry receptors.
Purpose of the Study:
- To investigate the role of heparan sulfate proteoglycans (HSPGs) and purinergic receptors (P2XRs) in hepatitis delta virus (HDV) entry into hepatocytes.
- To elucidate the specific molecular interactions governing HDV hepatocyte attachment and infection.
Main Methods:
- Utilized HepaRG cell line and primary human hepatocytes (PHH) susceptible to HBV/HDV infection.
- Assessed HDV entry inhibition using soluble glycosaminoglycans (GAGs), heparinase III treatment, sodium chlorate, and P2XR antagonists/agonists (charged and uncharged).
Main Results:
- HDV entry is dependent on the glycosaminoglycan (GAG) side chains of cellular HSPGs.
- Effects attributed to P2XRs were due to the negative charge of inhibitors, not direct receptor interaction.
- HDV infection was blocked by soluble GAGs, heparinase III, sodium chlorate, and highly sulfated P2XR antagonists, but not by uncharged P2XR modulators.
Conclusions:
- Hepatitis delta virus (HDV) infection requires binding to the carbohydrate side chains of hepatocyte-associated heparan sulfate proteoglycans (HSPGs) as attachment receptors.
- Purinergic receptors (P2XRs) are not actively involved in HBV/HDV entry.
- Findings clarify early viral entry mechanisms, crucial for understanding and potentially treating HBV/HDV co-infections.
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