Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques

Nat Commun. 2017 Dec 15;8(1):2146. doi: 10.1038/s41467-017-01953-y.


Hepatitis B virus (HBV) is a major global health concern, and the development of curative therapeutics is urgently needed. Such efforts are impeded by the lack of a physiologically relevant, pre-clinical animal model of HBV infection. Here, we report that expression of the HBV entry receptor, human sodium-taurocholate cotransporting polypeptide (hNTCP), on macaque primary hepatocytes facilitates HBV infection in vitro, where all replicative intermediates including covalently closed circular DNA (cccDNA) are present. Furthermore, viral vector-mediated expression of hNTCP on hepatocytes in vivo renders rhesus macaques permissive to HBV infection. These in vivo macaque HBV infections are characterized by longitudinal HBV DNA in serum, and detection of HBV DNA, RNA, and HBV core antigen (HBcAg) in hepatocytes. Together, these results show that expressing hNTCP on macaque hepatocytes renders them susceptible to HBV infection, thereby establishing a physiologically relevant model of HBV infection to study immune clearance and test therapeutic and curative approaches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • DNA, Viral / metabolism
  • Hepatitis B / genetics
  • Hepatitis B / metabolism
  • Hepatitis B / virology
  • Hepatitis B Core Antigens / metabolism
  • Hepatitis B virus / genetics
  • Hepatitis B virus / metabolism
  • Hepatitis B virus / physiology*
  • Hepatocytes / cytology
  • Hepatocytes / metabolism*
  • Hepatocytes / virology*
  • Host-Pathogen Interactions
  • Humans
  • Macaca mulatta
  • Organic Anion Transporters, Sodium-Dependent / genetics
  • Organic Anion Transporters, Sodium-Dependent / metabolism*
  • RNA, Viral / metabolism
  • Symporters / genetics
  • Symporters / metabolism*


  • DNA, Viral
  • Hepatitis B Core Antigens
  • Organic Anion Transporters, Sodium-Dependent
  • RNA, Viral
  • Symporters
  • sodium-bile acid cotransporter