J Bacteriol Virol.  2016 Dec;46(4):335-342. 10.4167/jbv.2016.46.4.335.

The Role of Sodium-taurocholate Co-transporting Polypeptide as a Receptor during HBV Infection

• Kim SY
• Jang E
• Inn KS

• KMID: 2366883
• DOI: http://doi.org/10.4167/jbv.2016.46.4.335

Abstract

According to World Health Organization, more than 200 million people suffer with chronic hepatitis caused by Hepatitis B virus (HBV) infection worldwide. Chronic hepatitis B causes various complications including liver cirrhosis and hepatocellular carcinoma and approximately 0.5~4.2 million deaths occur annually due to HBV infection. Current therapies such as antivirals and vaccine are often hampered by drug intolerance, side effects, and long-time medication, therefore, the development of powerful anti-HBV drugs is demanded. Recently, sodium taurocholate co-transporting polypeptide (NTCP) receptor was revealed to play a pivotal role in HBV entry into hepatocytes. Cell lines transfected with NTCP receptor enables to analyze HBV life cycle by inducing HBV infection stably, but in vivo models still have some limitations such as high costs, restrictive differentiation, and unveiled cofactors related to human NTCP. Therefore, it requires well-established in vivo models to develop and evaluate novel therapeutic agents targeting NTCP receptor, and viral entry inhibitors that inhibit the early step of viral infection are potent sufficient to substitute for existing antivirals.

Keyword

Hepatitis B virus; Receptor; Sodium-taurocholate co-transporting polypeptide; Entry

MeSH Terms

Antiviral Agents
Carcinoma, Hepatocellular
Cell Line
Hepatitis B virus
Hepatitis B, Chronic
Hepatitis, Chronic
Hepatocytes
Humans
Life Cycle Stages
Liver Cirrhosis
Taurocholic Acid
World Health Organization
Antiviral Agents
Taurocholic Acid

Figure

• 

  Figure 1. Structure of Hepatitis B virus. HBV consists of an outer envelope and inner nucleocapsid. The envelop contains HBsAg which com-prises three proteins; the small (S), middle (S+ preS2), large (S+preS2+preS1) surface protein. Among them, only the preS1 domain has an infectious capacity. The capsid encloses genomic DNA, DNA polymerase, HBeAg, and HBcAg.

• 

  Figure 2. Hepatitis B virus S protein structure. (A) HBsAg consists of three surface proteins. The small S antigen has only S domain and the middle S antigen harbors preS2 and S domains. The large S antigen contains preS1, preS2, and S domains. (B) Schematic structure of preS1-S2 domains. preS1 domain amino acids 2–77 are necessary for viral infection. Among amino acid 2–48, amino acid 9–18 are essential binding sites of HBsAg for NTCP receptor of human hepatocyte, and amino acid 28–48 are accessory parts. Both preS1 and preS2 domains are important for virion formation.

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  Figure 3. NTCP amino acid sequence homology between human and other species. (A) Identities and Homologies come from protein sequence Homo sapiens against Crab eating monkey, Rattus norvegicus and Mus musculus. (B) Schematic drawing of HBs domain of Homo sapiens, macaca fascicularis and mus musculus. Amino acid full sequence of Homo sapiens is in discord with that of macaca fascicularis and mus musculus. Amino acid 157–165 of macaca facicularis and amino acid 84–87 of mus musculus are different from Homo sapiens amino acids.

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  Figure 4. Schematic representation of the hepatitis B virus attachment. Heparan sulfate proteoglycan (HSPG) and Glypican5 (GPC5) help pre-S1 domain of HBsAg attach to NTCP receptor expressed in the surface of human hepatocyte.

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