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.DOI:http://dx.doi.org/10.7554/eLife.00049.001.
authors.affiliation: Graduate program in School of Life Sciences ,  Peking University ,  Beijing ,  China ; National Institute of Biological Sciences ,  Beijing ,  China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yan
authors.forename: Guocai
authors.initials: G
authors.lastname: Zhong
authors.forename: Guangwei
authors.initials: G
authors.lastname: Xu
authors.forename: Wenhui
authors.initials: W
authors.lastname: He
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Jing
authors.forename: Zhenchao
authors.initials: Z
authors.lastname: Gao
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Yonghe
authors.initials: Y
authors.lastname: Qi
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.forename: Haimin
authors.initials: H
authors.lastname: Wang
authors.forename: Liran
authors.initials: L
authors.lastname: Fu
authors.forename: Mei
authors.initials: M
authors.lastname: Song
authors.forename: Pan
authors.initials: P
authors.lastname: Chen
authors.forename: Wenqing
authors.initials: W
authors.lastname: Gao
authors.forename: Bijie
authors.initials: B
authors.lastname: Ren
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Sun
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Feng
authors.forename: Jianhua
authors.initials: J
authors.lastname: Sui
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D015870:Gene Expression; D006515:Hepatitis B virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003698:Hepatitis Delta Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008969:Molecular Sequence Data; D029363:Organic Anion Transporters, Sodium-Dependent / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D055668:Photochemical Processes; D061251:Primary Cell Culture; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D027981:Symporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013656:Taurocholic Acid / Q000378:metabolism; D014417:Tupaia; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D029363:Organic Anion Transporters, Sodium-Dependent; D010455:Peptides; D011991:Receptors, Virus; D027981:Symporters; D014759:Viral Envelope Proteins; C071908:sodium-bile acid cotransporter; D013656:Taurocholic Acid