Peptides that block hepatitis B virus assembly: analysis by cryomicroscopy, mutagenesis and transfection.
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.
Böttcher
B
B
Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Tsuji
N
N
Takahashi
H
H
Dyson
M R
MR
Zhao
S
S
Crowther
R A
RA
Murray
K
K
D000998:Antiviral Agents / Q000378:metabolism*; D001665:Binding Sites; D003432:Cross-Linking Reagents; D020285:Cryoelectron Microscopy; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000378:metabolism; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000502:physiology; D006801:Humans; D016296:Mutagenesis; D010455:Peptides / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D019065:Virus Assembly
D000998:Antiviral Agents; D003432:Cross-Linking Reagents; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D010455:Peptides