title: Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus.
abstract: Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157-165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV.
authors.affiliation: Graduate program in School of Life Sciences, Peking University, Beijing, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yan
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Guocai
authors.initials: G
authors.lastname: Zhong
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Xu
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: He
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Jing
authors.affiliation: Graduate program in School of Life Sciences, Peking University, Beijing, China.
authors.forename: Zhenchao
authors.initials: Z
authors.lastname: Gao
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Yonghe
authors.initials: Y
authors.lastname: Qi
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Haimin
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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: Mei
authors.initials: M
authors.lastname: Song
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Chen
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Gao
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Bijie
authors.initials: B
authors.lastname: Ren
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Feng
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Sui
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004198:Disease Susceptibility; D006509:Hepatitis B / Q000473:pathology / Q000821:virology; D006515:Hepatitis B virus / Q000378:metabolism*; D003699:Hepatitis D / Q000473:pathology / Q000821:virology; D003698:Hepatitis Delta Virus / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D029363:Organic Anion Transporters, Sodium-Dependent / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism*; D015203:Reproducibility of Results; D027981:Symporters / Q000737:chemistry / Q000378:metabolism*; D014418:Tupaiidae; D014771:Virion / Q000378:metabolism
chemical_list: D008024:Ligands; D029363:Organic Anion Transporters, Sodium-Dependent; D011991:Receptors, Virus; D027981:Symporters; C071908:sodium-bile acid cotransporter
keywords: Sodium taurocholate cotransporting polypeptide; biochemistry; hepatitis B virus; hepatitis D virus; infectious disease; liver; microbiology; receptor; virus infection; viruses