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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Burwitz, BJ; Wettengel, JM; Mück-Häusl, MA; Ringelhan, M; Ko, C; Festag, MM; Hammond, KB; Northrup, M; Bimber, BN; Jacob, T; Reed, JS; Norris, R; Park, B; Moller-Tank, S; Esser, K; Greene, JM; Wu, HL; Abdulhaqq, S; Webb, G; Sutton, WF; Klug, A; Swanson, T; Legasse, AW; Vu, TQ; Asokan, A; Haigwood, NL; Protzer, U; Sacha, JB

Published Date

  • December 15, 2017

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • 2146 -

PubMed ID

  • 29247188

Pubmed Central ID

  • 29247188

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

International Standard Serial Number (ISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-017-01953-y

Language

  • eng