Mapping of the Hepatitis B Virus Attachment Site by Use of Infection-Inhibiting preS1 Lipopeptides and Tupaia Hepatocytes
| Autor: | Aiste Bulavaite, Dieter Glebe, Wolfram H. Gerlich, Eva V. Knoop, Stefanie Grün, Kestutis Sasnauskas, Stephan Urban, Nilgün Cag, Peter Krass |
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| Rok vydání: | 2005 |
| Předmět: |
Hepatitis B virus
HBsAg Lipoproteins Tupaia Molecular Sequence Data medicine.disease_cause Myristic Acid Virus Epitope medicine Animals Humans Amino Acid Sequence Protein Precursors Cells Cultured chemistry.chemical_classification Hepatitis B Surface Antigens Hepatology biology Virion Gastroenterology Chromosome Mapping Hepatitis B biology.organism_classification medicine.disease Virology Molecular biology Protein Structure Tertiary Amino acid Kinetics chemistry HBeAg Hepatocytes Protein Binding |
| Zdroj: | Gastroenterology. 129:234-245 |
| ISSN: | 0016-5085 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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