Woodchuck sodium taurocholate cotransporting polypeptide supports low-level hepatitis B and D virus entry

• Published in: Virology (New York, N.Y.) Vol. 505; pp. 1 - 11
• Main Authors: Fu, Liran, Hu, Hongjie, Liu, Yang, Jing, Zhiyi, Li, Wenhui
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2017
• Subjects: Amino Acid Sequence - genetics; Animals; Binding Sites - genetics; Cell Line, Tumor; Cloning, Molecular; Hep G2 Cells; Hepatitis B virus; Hepatitis B virus - metabolism; Hepatitis D virus; Hepatitis Delta Virus - metabolism; Hepatocytes - virology; Host Specificity - genetics; Humans; Infectious Disease; Liver - metabolism; Liver - virology; Male; Marmota - virology; Organic Anion Transporters, Sodium-Dependent - genetics; Organic Anion Transporters, Sodium-Dependent - metabolism; Protein Binding - genetics; Receptors, Virus - genetics; Receptors, Virus - metabolism; Sodium taurocholate cotransporting polypeptide; Symporters - genetics; Symporters - metabolism; Viral entry; Virus Internalization; Woodchuck; Hepatitis D virus; Viral entry; Sodium taurocholate cotransporting polypeptide; Woodchuck; Hepatitis B virus
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2017.02.006

Abstract Sodium taurocholate cotransporting polypeptide (NTCP) is the functional receptor for human hepatitis B virus (HBV) and its satellite hepatitis D virus (HDV). Species barriers to HBV/HDV infection are mainly determined at entry level by variations in the sequences of particular NTCP orthologs. In this study, we sought to determine whether the NTCP ortholog in woodchuck ( Marmota monax ), woodchuck NTCP (wNTCP) supports viral infection. We found that wNTCP is capable of supporting HBV/HDV infection in HepG2 cells, but to much lower extent than human NTCP (hNTCP), which is about 90% reduction of hNTCP. Comprehensive site-directed mutagenesis mapping of hNTCP and wNTCP revealed that the residue at position 263 is a novel site crucial for viral entry. The important role of site 263 in infection is conserved among NTCP orthologs and may therefore be a potential target for blocking the viral entry.