title: NTCP and beyond: opening the door to unveil hepatitis B virus entry.
abstract: Chronic hepatitis B virus (HBV) infection, affecting approximately 240 million people worldwide, is a major public health problem that elevates the risk of developing liver cirrhosis and hepatocellular carcinoma. Given that current anti-HBV drugs are limited to interferon-based regimens and nucleos(t)ide analogs, the development of new anti-HBV agents is urgently needed. The viral entry process is generally an attractive target implicated in antiviral strategies. Using primary cells from humans and Tupaia belangeri, as well as HepaRG cells, important determinants of viral entry have been achieved. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was identified as an HBV entry receptor and enabled the establishment of a susceptible cell line that can efficiently support HBV infection. This finding will allow a deeper understanding of the requirements for efficient HBV infection, including the elucidation of the molecular entry mechanism. In addition, pharmacological studies suggest that NTCP is able to serve as a therapeutic target. This article summarizes our current knowledge on the mechanisms of HBV entry and the role of NTCP in this process.
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, 162-8640 Tokyo, Japan. kwatashi@nih.go.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Watashi
authors.affiliation: Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Im Neuenheimer Feld 345, D-69120 Heidelberg, Germany. stephan.urban@med.uni-heidelberg.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Urban
authors.affiliation: National Institute of Biological Sciences, No.7 Science Park Road, ZGC Life Science Park, Changping, 102206 Beijing, China. liwenhui@nibs.ac.cn.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, 162-8640 Tokyo, Japan. wakita@nih.go.jp.
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D006509:Hepatitis B / Q000378:metabolism / Q000473:pathology; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D029363:Organic Anion Transporters, Sodium-Dependent / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011498:Protein Precursors / Q000378:metabolism; D027981:Symporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D029363:Organic Anion Transporters, Sodium-Dependent; D011498:Protein Precursors; D027981:Symporters; C050806:presurface protein 1, hepatitis B surface antigen; C071908:sodium-bile acid cotransporter