Clin Mol Hepatol.  2015 Sep;21(3):193-199. 10.3350/cmh.2015.21.3.193.

From DCPD to NTCP: The long journey towards identifying a functional hepatitis B virus receptor

• Li J
• Tong S

• KMID: 2351018
• DOI: http://doi.org/10.3350/cmh.2015.21.3.193

Abstract

Hepatitis B virus (HBV) is the prototype of hepatotropic DNA viruses (hepadnaviruses) infecting a wide range of human and non-human hosts. Previous studies with duck hepatitis B virus (DHBV) identified duck carboxypeptidase D (dCPD) as a host specific binding partner for full-length large envelope protein, and p120 as a binding partner for several truncated versions of the large envelope protein. p120 is the P protein of duck glycine decarboxylase (dGLDC) with restricted expression in DHBV infectible tissues. Several lines of evidence suggest the importance of dCPD, and especially p120, in productive DHBV infection, although neither dCPD nor p120 cDNA could confer susceptibility to DHBV infection in any cell line. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a binding partner for the N-terminus of HBV large envelope protein. Importantly, knock down and reconstitution experiments unequivocally demonstrated that NTCP is both necessary and sufficient for in vitro infection by HBV and hepatitis delta virus (HDV), an RNA virus using HBV envelope proteins for its transmission. What remains unclear is whether NTCP is the major HBV receptor in vivo. The fact that some HBV patients are homozygous with an NTCP mutation known to abolish its receptor function suggests the existence of NTCP-independent pathways of HBV entry. Also, NTCP very likely mediates just one step of the HBV entry process, with additional co-factors for productive HBV infection still to be discovered. NTCP offers a novel therapeutic target for the control of chronic HBV infection.

Keyword

Hepatitis B virus; Carboxypeptidase D; Glycine decarboxylase; heparan sulfate proteoglycans; Sodium taurocholate cotransporting polypeptide

MeSH Terms

Animals
Carboxypeptidases/genetics/*metabolism
Gene Products, pol/genetics/metabolism
Heparan Sulfate Proteoglycans/metabolism
Hepatitis B virus/*physiology
Hepatocytes/metabolism/virology
Organic Anion Transporters, Sodium-Dependent/antagonists & inhibitors/genetics/metabolism
RNA Interference
Symporters/antagonists & inhibitors/genetics/metabolism
Viral Envelope Proteins/metabolism
Virus Internalization
Carboxypeptidases
Gene Products, pol
Heparan Sulfate Proteoglycans
Organic Anion Transporters, Sodium-Dependent
Symporters
Viral Envelope Proteins