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  • The EMBO Journal (1998) 17, 6839 - 6845
  • doi:10.1093/emboj/17.23.6839

Peptides that block hepatitis B virus assembly: analysis by cryomicroscopy, mutagenesis and transfection

B. Böttcher1,2,6, N. Tsuji3,6, H. Takahashi3, M.R. Dyson4,5, S. Zhao4, R.A. Crowther1 and K. Murray4

  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; Accepted 25 September 1998; Revised 25 September 1998

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.

  • Keywords:

    • difference imaging,
    • electron cryomicroscopy,
    • hepatitis B virus,
    • peptide inhibitors,
    • virus assembly