Pre-s1 Antigen-Dependent Infection of Tupaia Hepatocyte Cultures With Human Hepatitis B Virus

J Virol. 2003 Sep;77(17):9511-21. doi: 10.1128/jvi.77.17.9511-9521.2003.

Abstract

The susceptibility of the tree shrew Tupaia belangeri to human hepatitis B virus (HBV) has been demonstrated both in vivo and in vitro. In this study, we show that purified HBV infects primary T. belangeri hepatocyte cultures in a very specific manner, as detected by HBV covalently closed circular DNA, mRNA, HBV e antigen, and HBsAg production. A monoclonal antibody (MAb), MA18/7, directed against the pre-S1 domain of the large HBs protein, which has been shown to neutralize infectivity of HBV for primary human hepatocytes, also blocked infection of primary Tupaia hepatocytes. MAbs against the pre-S2 domain of HBs inhibited infection only partially, whereas an S MAb and polyvalent anti-HBs antibodies neutralized infection completely. Thus, both pre-S1 and S antigens are necessary for infection in the tupaia. Using subviral particles, >70% of primary Tupaia hepatocytes are capable of specific binding of pre-S1-rich HBsAg, showing localization in distinct membrane areas. The data show that the early steps of HBV infection in Tupaia hepatocyte cultures are comparable to those in the human system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cells, Cultured
  • DNA, Viral / genetics
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B Surface Antigens / physiology*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B virus / pathogenicity*
  • Hepatitis B virus / physiology
  • Hepatocytes / virology*
  • Humans
  • Kinetics
  • Neutralization Tests
  • Protein Precursors / genetics
  • Protein Precursors / physiology*
  • Tupaia
  • Virus Replication

Substances

  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Protein Precursors
  • presurface protein 1, hepatitis B surface antigen