Analysis of HIV-1 fusion peptide inhibition by synthetic peptides from E1 protein of GB virus C

作者：Jesus Sanchez Martin Maria; Hristova Kalina; Pujol Montserrat; Gomara Maria J; Haro Isabel; Asuncion Alsina M; Antonia Busquets M

来源：Journal of Colloid and Interface Science, 2011, 360(1): 124-131.

DOI：10.1016/j.jcis.2011.04.053

• HIV-1 FP inhibition
• Hepatitis G virus
• Peptide synthesis
• Bilayers as model membranes
• Giant unilamellar vesicles
• Confocal microscopy

The aim of this study was to identify proteins that could inhibit the activity of the peptide sequence representing the N-terminal of the surface protein gp41 of HIV, corresponding to the fusion peptide of the virus (HIV-1 FP). To do this we synthesized and studied 58 peptides corresponding to the envelope protein El of the hepatitis G virus (GBV-C).
Five of the El synthetic peptides: NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCL VALGCTICTD (P10), QAGLAVRPGKSAAQLVGE (P18) and AQLVGELGSLYGPLSVSA (P22) were capable of inhibiting the leakage of vesicular contents caused by HIV-1 FP. A series of experiments were carried out to determine how these El peptides interact with HIV-1 FP. Our studies analyzed the interactions with and without the presence of lipid membranes. Isothermal titration calorimetry revealed that the binding of P7, P18 and P22 peptides to HIV-1 FP is strongly endothermic, and that binding is entropy-driven. Gibbs energy for the process indicates a spontaneous binding between El peptides and HIV-1 FP. Moreover, confocal microscopy of Giant Unilamellar Vesicles revealed that the disruption of the lipid bilayer by HIV-1 FP alone was inhibited by the presence of any of the five selected peptides.
Our results highlight that these El synthetic peptides could be involved in preventing the entry of HIV-1 by binding to the HIV-1 FP. Therefore, the continued study into the interaction between GBV-C peptides and HIV-1 FP could lead to the development of new therapeutic agents for the treatment of AIDS.

• 出版日期2011-8-1