Characterization of a hepatitis B and hepatitis delta virus receptor binding site
| Autor: | Stephan Urban, Kerry E Mills, Philippe Gripon, Petra Simon, Martina Schnölzer, Matthias Engelke, Stefan Seitz |
|---|---|
| Přispěvatelé: | Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UR) |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
MESH: Amino Acid Sequence
medicine.disease_cause Myristic Acid MESH: Peptide Mapping MESH: Protein Structure Tertiary 0302 clinical medicine Orthohepadnavirus Viral Envelope Proteins Peptide sequence Conserved Sequence Glutathione Transferase 0303 health sciences MESH: Conserved Sequence biology MESH: Escherichia coli Virus receptor Hepatitis B MESH: Lipoproteins Hepatitis D MESH: Amino Acid Substitution 3. Good health MESH: Hepatitis B virus [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology Receptors Virus 030211 gastroenterology & hepatology Hepatitis Delta Virus Hepatitis B virus MESH: Cell Line Tumor Lipoproteins Recombinant Fusion Proteins Molecular Sequence Data Peptide Mapping Hepatitis B virus PRE beta Hepatitis B Virus Duck Viral Matrix Proteins 03 medical and health sciences MESH: Hepatitis B Virus Duck Cell Line Tumor medicine Escherichia coli MESH: Recombinant Fusion Proteins Humans Point Mutation Amino Acid Sequence 030304 developmental biology MESH: Point Mutation MESH: Viral Matrix Proteins MESH: Hepatitis D MESH: Glutathione Transferase Binding Sites MESH: Humans MESH: Molecular Sequence Data Hepatology MESH: Hepatitis B medicine.disease biology.organism_classification Virology MESH: Hepatitis Delta Virus MESH: Receptors Virus Protein Structure Tertiary Hepadnaviridae Amino Acid Substitution MESH: Binding Sites MESH: Myristic Acid MESH: Viral Envelope Proteins |
| Zdroj: | Hepatology Hepatology, Wiley-Blackwell, 2006, 43 (4), pp.750-60. ⟨10.1002/hep.21112⟩ Hepatology, 2006, 43 (4), pp.750-60. ⟨10.1002/hep.21112⟩ |
| ISSN: | 0270-9139 1527-3350 |
| DOI: | 10.1002/hep.21112⟩ |
| Popis: | International audience; Insights into the early infection events of the human hepatitis B (HBV) and hepatitis delta virus (HDV) have been limited because of the lack of a cell culture system supporting the full replication cycle for these important pathogens. The human hepatoma cell line HepaRG allows the experimental induction of a differentiated state, thereby gaining susceptibility toward HBV and HDV infection. We recently identified HBV envelope protein-derived lipopeptides comprising amino acids 2 though 48 of the preS-domain of the L-surface protein, which block infection already at picomolar concentrations. To map the responsible sequence for the peptides' activity we describe an Escherichia coli expression system that permits myristoylation and investigated recombinant HBVpreS-GST fusion proteins with deletion- and point-mutations for their ability to prevent HBV and HDV infection. We found that (1) a myristoylated HBVpreS/2-48-GST fusion protein efficiently interferes with HBV infection of HepaRG cells; (2) deletions and point mutations in the highly conserved preS1 sequence between amino acids 11 through 21 result in the loss of infection inhibition activity; (3) hepatitis B viruses carrying single amino acid exchanges within this region lose infectivity; and (4) HDV infection of HepaRG cells can be inhibited by myristoylated HBVpreS peptides with the same specificity. In conclusion, HBV and HDV use at least one common step to enter hepatocytes and require a highly conserved preS1-sequence within the L-protein. This step is exceptionally sensitive toward inactivation by acylated HBVpreS1 peptides, which therefore represent a novel group of entry inhibitors that could be used for the treatment of hepatitis B and D. |
| Databáze: | OpenAIRE |
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