Sodium taurocholate cotransporting polypeptide mediates woolly monkey hepatitis B virus infection of Tupaia hepatocytes

J Virol. 2013 Jun;87(12):7176-84. doi: 10.1128/JVI.03533-12. Epub 2013 Apr 17.

Abstract

Primary Tupaia hepatocytes (PTHs) are susceptible to woolly monkey hepatitis B virus (WMHBV) infection, but the identity of the cellular receptor(s) mediating WMHBV infection of PTHs remains unclear. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was identified as a functional receptor for human hepatitis B virus (HBV) infection of primary human and Tupaia hepatocytes. In this study, a synthetic pre-S1 peptide from WMHBV was found to bind specifically to cells expressing Tupaia NTCP (tsNTCP) and it efficiently blocked WMHBV entry into PTHs; silencing of tsNTCP in PTHs significantly inhibited WMHBV infection. Ectopic expression of tsNTCP rendered HepG2 cells susceptible to WMHBV infection. These data demonstrate that tsNTCP is a functional receptor for WMHBV infection of PTHs. The result also indicates that NTCP's orthologs likely act as a common cellular receptor for all known primate hepadnaviruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Atelinae / virology*
  • Cells, Cultured
  • Hepadnaviridae / genetics
  • Hepadnaviridae / metabolism
  • Hepadnaviridae / pathogenicity*
  • Hepadnaviridae Infections / virology
  • Hepatitis B Surface Antigens / chemistry
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B Surface Antigens / metabolism
  • Hepatocytes / virology*
  • Humans
  • Molecular Sequence Data
  • Organic Anion Transporters, Sodium-Dependent / metabolism*
  • Protein Precursors / chemistry
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Receptors, Virus / metabolism*
  • Symporters / metabolism*
  • Tupaia / virology*

Substances

  • Hepatitis B Surface Antigens
  • Organic Anion Transporters, Sodium-Dependent
  • Protein Precursors
  • Receptors, Virus
  • Symporters
  • presurface protein 1, hepatitis B surface antigen
  • sodium-bile acid cotransporter