Synthetic peptide from the V3 loop consensus motif with a potent anti-HIV activity inhibits ristocetin-mediated vWF-GPIb interaction.
The V3 loop consensus motif. Arg-Gly-Pro-Gly-Arg-Ala-Phe-Val-Thr-Ile (HIV-1 IIIB), inhibits an interaction of HIV with CD4-positive lymphocytes. Recently, both proline-rich peptides and peptides containing proline-glycine loops (beta-turns) form a complex with ristocetin dimers. These peptides interact with ristocetin-loaded platelet membrane glycoprotein (GP) Ib and act as inhibitors of von Willebrand factor (vWF)-GPIb interaction by preventing the subsequent formation of ristocetin dimer bridges. The Pro-Gly sequence is also present in the V3 loop consensus motif, Arg-Gly-Pro-Gly-Arg-Ala-Phe-Val-Thr-Ile (HIV-1 IIIB). In this report, we have evaluated the effect of the HIV-1 IIIB peptide on vWF binding to GPIb. This peptide only inhibited vWF binding to GPIb as well as platelet aggregation in the presence of ristocetin while it had no effect on botrocetin-mediated vWF interaction with platelets. The peptide inhibited a binding of anti-vWF monoclonal antibody (RG-46) to immobilized vWF. Furthermore, ristocetin inhibited the binding of HIV-1 IIIB peptide to immobilized CXC-chemokine receptor-4 (CXCR-4) peptide. These results indicate that ristocetin may prevent HIV infection and would be useful a tool to understand the mechanism of HIV tissue tropism and infection.
Mohri
H
H
First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Asakura
Y
Y
Fukushima
J
J
Kawamoto
S
S
Okubo
T
T
Okuda
K
K
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors*; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016384:Consensus Sequence; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D012310:Ristocetin / Q000037:antagonists & inhibitors*; D014841:von Willebrand Factor / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D009842:Oligopeptides; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D012310:Ristocetin