title: Woodchuck sodium taurocholate cotransporting polypeptide supports low-level hepatitis B and D virus entry.
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.
authors.affiliation: Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; National Institute of Biological Sciences, Beijing, China.
authors.forename: Liran
authors.initials: L
authors.lastname: Fu
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Hu
authors.affiliation: National Institute of Biological Sciences, Beijing, China; Graduate Program in School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Jing
authors.affiliation: Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; National Institute of Biological Sciences, Beijing, China; Graduate Program in School of Life Sciences, Tsinghua University, Beijing, China. Electronic address: liwenhui@nibs.ac.cn.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000378:metabolism*; D003698:Hepatitis Delta Virus / Q000378:metabolism*; D022781:Hepatocytes / Q000821:virology; D058507:Host Specificity / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000821:virology; D008297:Male; D008392:Marmota / Q000821:virology; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics* / Q000378:metabolism; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D029363:Organic Anion Transporters, Sodium-Dependent; D011991:Receptors, Virus; D027981:Symporters; C071908:sodium-bile acid cotransporter
keywords: Hepatitis B virus; Hepatitis D virus; Sodium taurocholate cotransporting polypeptide; Viral entry; Woodchuck