Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes

Gastroenterology. 2005 Jul;129(1):234-45. doi: 10.1053/j.gastro.2005.03.090.

Abstract

Background & aims: Studies on the early steps in the life cycle of hepatitis B virus have been hampered by the lack of readily available target cells. In this study, we mapped a defined virus attachment site to primary hepatocytes that is essential for infection.

Methods: We used purified virus particles from human carrier plasma as an inoculum and primary cultures of tupaia hepatocytes as susceptible target cells and studied the inhibitory effect of amino-terminally acylated preS1-derived lipopeptides on infection interference.

Results: Infectivity of virus could be blocked efficiently in this system by amino-terminally acylated peptides containing amino acids 2-18 from the preS1 domain. The addition of amino acids 28-48 enhanced the inhibitory capacity, whereas amino acids 49-78 did not contribute to inhibition. Myristoylated preS1 peptides 2-48 bound strongly to tupaia hepatocytes but not to nonhepatic cells or rodent hepatocytes and thereby inhibited infection even at concentrations of 1 nmol/L completely. Particles consisting only of the small hepatitis B surface protein-the active component of current hepatitis B vaccines-did not bind at all to tupaia hepatocytes, but the addition of the preS1 domain to the particles allowed binding.

Conclusions: The preS1 sequence 2-48 mediates attachment of the virus to its target cells, whereas the small surface protein seems to be involved in other steps. These findings indicate that the current subunit hepatitis B vaccines may be improved by the addition of distinct preS1 epitopes. Moreover, preS1 lipopeptides are promising candidates for specific antiviral therapy against hepatitis B infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Chromosome Mapping
  • Hepatitis B / drug therapy
  • Hepatitis B / prevention & control
  • Hepatitis B / virology*
  • Hepatitis B Surface Antigens / chemistry
  • Hepatitis B Surface Antigens / genetics*
  • Hepatitis B Surface Antigens / metabolism*
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / metabolism
  • Hepatocytes / cytology
  • Hepatocytes / virology
  • Humans
  • Kinetics
  • Lipoproteins / metabolism
  • Lipoproteins / pharmacology
  • Molecular Sequence Data
  • Myristic Acid / metabolism
  • Protein Binding
  • Protein Precursors / chemistry
  • Protein Precursors / genetics*
  • Protein Precursors / metabolism*
  • Protein Structure, Tertiary
  • Tupaia
  • Virion / growth & development
  • Virion / physiology

Substances

  • Hepatitis B Surface Antigens
  • Lipoproteins
  • Protein Precursors
  • presurface protein 1, hepatitis B surface antigen
  • Myristic Acid