A peptide inhibitor of HIV-1 assembly in vitro.
Formation of infectious HIV-1 involves assembly of Gag polyproteins into immature particles and subsequent assembly of mature capsids after proteolytic disassembly of the Gag shell. We report a 12-mer peptide, capsid assembly inhibitor (CAI), that binds the capsid (CA) domain of Gag and inhibits assembly of immature- and mature-like capsid particles in vitro. CAI was identified by phage display screening among a group of peptides with similar sequences that bind to a single reactive site in CA. Its binding site was mapped to CA residues 169-191, with an additional contribution from the last helix of CA. This result was confirmed by a separate X-ray structure analysis showing that CAI inserts into a conserved hydrophobic groove and alters the CA dimer interface. The CAI binding site is a new target for antiviral development, and CAI is the first known inhibitor directed against assembly of immature HIV-1.
Sticht
Jana
J
Department of Virology, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany.
Humbert
Michael
M
Findlow
Stuart
S
Bodem
Jochen
J
Müller
Barbara
B
Dietrich
Ursula
U
Werner
Jörn
J
Kräusslich
Hans-Georg
HG
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002213:Capsid / Q000502:physiology* / Q000648:ultrastructure; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D019151:Peptide Library; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly / Q000502:physiology*
D000998:Antiviral Agents; D036022:Capsid Proteins; D015683:Gene Products, gag; D019151:Peptide Library; D010455:Peptides