From DCPD to NTCP: The long journey towards identifying a functional hepatitis B virus receptor.
10.3350/cmh.2015.21.3.193
- Author:
Jisu LI
1
;
Shuping TONG
Author Information
1. Liver Research Center, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, USA. Ji_su_li_md@brown.edu, shuping_tong_md@brown.edu
- Publication Type:Research Support, N.I.H., Extramural ; Review
- Keywords:
Hepatitis B virus;
Carboxypeptidase D;
Glycine decarboxylase;
heparan sulfate proteoglycans;
Sodium taurocholate cotransporting polypeptide
- MeSH:
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
- From:Clinical and Molecular Hepatology
2015;21(3):193-199
- CountryRepublic of Korea
- Language:English
-
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.
