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Gastroenterology. 2005 Jul;129(1):234-45.

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

Author information

1
Institute of Medical Virology, Justus-Liebig University Giessen, Germany. dieter.glebe@ciro.med.uni-giessen.de

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.

PMID:
16012950
DOI:
10.1053/j.gastro.2005.03.090
[Indexed for MEDLINE]

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