Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes.
OBJECTIVE
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.
Glebe
Dieter
D
Institute of Medical Virology, Justus-Liebig University Giessen, Germany. dieter.glebe@ciro.med.uni-giessen.de
Urban
Stephan
S
Knoop
Eva V
EV
Cag
Nilgün
N
Krass
Peter
P
Grün
Stefanie
S
Bulavaite
Aiste
A
Sasnauskas
Kestutis
K
Gerlich
Wolfram H
WH
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002874:Chromosome Mapping; D006509:Hepatitis B / Q000188:drug therapy / Q000517:prevention & control / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics* / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000821:virology; D006801:Humans; D007700:Kinetics; D008074:Lipoproteins / Q000378:metabolism / Q000494:pharmacology; D008969:Molecular Sequence Data; D019814:Myristic Acid / Q000378:metabolism; D011485:Protein Binding; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D014417:Tupaia; D014771:Virion / Q000254:growth & development / Q000502:physiology
D006514:Hepatitis B Surface Antigens; D008074:Lipoproteins; D011498:Protein Precursors; C050806:presurface protein 1, hepatitis B surface antigen; D019814:Myristic Acid