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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
Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus
Huan Yan1, Guocai Zhong, Guangwei Xu
1Graduate program in School of Life Sciences , Peking University , Beijing , China ; National Institute of Biological Sciences , Beijing , China.
Elife
|November 15, 2012
Summary
Hepatitis B virus (HBV) and hepatitis D virus (HDV) use sodium taurocholate cotransporting polypeptide (NTCP) to infect liver cells. Identifying NTCP as the HBV/HDV receptor is crucial for developing new antiviral therapies.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Hepatitis B virus (HBV) and hepatitis D virus (HDV) infections pose significant global health challenges.
- Viral entry into host cells is mediated by viral envelope proteins, with the HBV pre-S1 domain being critical for receptor binding.
- The specific host cell receptor for HBV and HDV has remained unidentified.
Purpose of the Study:
- To identify the host cell receptor(s) responsible for HBV and HDV entry.
- To elucidate the interaction between HBV envelope proteins and potential cellular receptors.
Main Methods:
- Utilized near zero distance photo-cross-linking and tandem affinity purification to identify interacting proteins.
- Employed gene silencing and exogenous expression techniques to assess the role of the identified receptor.
- Performed site-directed mutagenesis to confirm receptor function.
Main Results:
- Identified sodium taurocholate cotransporting polypeptide (NTCP), a liver-expressed transporter, as the specific binding partner for the HBV pre-S1 domain.
- Demonstrated that NTCP silencing inhibits HBV and HDV infection.
- Showed that NTCP expression confers susceptibility to HBV and HDV infection in non-susceptible cells, and that specific amino acid substitutions in NTCP restore this function.
Conclusions:
- Sodium taurocholate cotransporting polypeptide (NTCP) is confirmed as the functional cellular receptor for both hepatitis B virus and hepatitis D virus.
- This discovery opens new avenues for therapeutic strategies targeting viral entry and infection.
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