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

eLife ◽  
2012 ◽  
Vol 1 ◽  
Author(s):  
Huan Yan ◽  
Guocai Zhong ◽  
Guangwei Xu ◽  
Wenhui He ◽  
Zhiyi Jing ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Viral Infections ◽  
Affinity Purification ◽  
Severe Disease ◽  
Sodium Taurocholate ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Hepatitis D ◽  
Human Hepatitis ◽  
Functional Receptor

Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157–165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV.

Sodium Taurocholate Cotransporting Polypeptide Acts as a Receptor for Hepatitis B and D Virus

2015 ◽  
Vol 33 (3) ◽  
pp. 388-396 ◽  
Author(s):  
Huan Yan ◽  
Wenhui Li
Keyword(s):  
Bile Acid ◽  
Hepatitis B ◽  
Bile Acids ◽  
Viral Entry ◽  
Viral Infections ◽  
Sodium Taurocholate ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Hepatitis D ◽  
Hdv Infection

Infection of hepatitis B virus (HBV) remains a major public health problem worldwide. Understanding the viral infection and developing antivirals against HBV have been hampered by the lack of convenient culture systems and animal models for the infection. Sodium taurocholate cotransporting polypeptide (NTCP), a key bile acid transporter expressed in liver, was recently identified as a critical receptor for viral entry of HBV and its satellite virus hepatitis D virus (HDV). This finding enabled a reliable cell culture system for the viruses. Detailed studies have shown that NTCP is the major determinant for the species specificity of HBV and HDV at entry level. NTCP is responsible for most sodium-dependent bile salt uptake in liver. The molecular determinant critical for HBV/HDV infection overlaps with that for bile acids transporting on NTCP. We evaluated bile acids as potential antivirals for HBV and HDV infection, and developed bile acid derivatives that effectively block taurocholate transporting as well as viral infections. The discovery that NTCP acts as a receptor for HBV has opens a new door for future studies towards the ultimate goal of curative treatment of HBV infection.

scholarly journals Correction: Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Huan Yan ◽  
Guocai Zhong ◽  
Guangwei Xu ◽  
Wenhui He ◽  
Zhiyi Jing ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Sodium Taurocholate ◽  
Human Hepatitis ◽  
Functional Receptor
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