Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus

Area of Science:

• Hepatology
• Virology
• Molecular Biology

Background:

• Hepatitis B virus (HBV) and hepatitis D virus (HDV) infections pose significant global health challenges.
• The cellular entry mechanisms for HBV and HDV, particularly the specific host cell receptors, remain largely unidentified.
• The pre-S1 domain of the HBV large envelope protein is known to be critical for viral attachment and entry.

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 the identified receptor.

Main Methods:

• Utilized near-zero distance photo-cross-linking and tandem affinity purification to identify protein interactions.
• Employed gene silencing (siRNA) to assess the role of the candidate receptor in viral infection.
• Used cell culture models, including hepatocarcinoma cells, to test viral infectivity upon receptor manipulation.

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 is essential for HBV and HDV cellular entry; silencing NTCP inhibited infection, while its expression conferred susceptibility.
• Showcased that specific amino acid substitutions in NTCP can restore its ability to support viral entry, confirming its functional role.

Conclusions:

• Sodium taurocholate cotransporting polypeptide (NTCP) serves as the functional receptor for both hepatitis B virus (HBV) and hepatitis D virus (HDV).
• This discovery provides a critical target for developing novel antiviral strategies against HBV and HDV infections.