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| The EMBO Journal
(1998) 17, 6839–6845, doi:10.1093/emboj/17.23.6839 |
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| Peptides that block hepatitis B virus assembly: analysis by cryomicroscopy, mutagenesis and transfection |
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| B. Böttcher1, 2, 6, N. Tsuji3, 6, H. Takahashi3, M.R. Dyson4, 5, S. Zhao4, R.A. Crowther1 and K. Murray4 |
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1 Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK 2 Present address: Institut für Physikalische Chemie, Universität Freiburg, Albertstrasse 23a, D-79104 Freiburg, Germany 3 Gastrointestinal Unit, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, USA 4 Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, UK 5 Present address: Peptide Therapeutics, 321 Cambridge Science Park, Milton Road, Cambridge CB4 4WG, UK 6 B.Böttcher and N.Tsuji contributed equally to this work Received 22 July 1998; Revised 25 September 1998; Accepted 25 September 1998. |
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| Abstract |
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| Peptides selected to bind to hepatitis B virus (HBV) core protein block interaction with the long viral surface antigen (L-HBsAg) in vitro. High resolution electron cryomicroscopy showed that one such peptide binds at the tips of the spikes of the core protein shell. The peptides contain two basic residues; changing either of two acidic residues at the spike tip to an alanine greatly reduced the binding affinity. Transfection of hepatoma cells with a replication-competent HBV plasmid gave significantly reduced production of virus in the presence of peptide, in a dose-dependent manner. These experiments show that the interaction of L-HBsAg with core particles is critical for HBV assembly, and give proof of principle for its disruption in vivo by small molecules. |
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| Keywords: difference imaging, electron cryomicroscopy, hepatitis B virus, peptide inhibitors, virus assembly |
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