PLENARY PAPER A Synthetic Peptide Derived From Human Immunodeficiency Virus Type 1 gp120 Downregulates the Expression and Function of Chemokine Receptors CCR5 and CXCR4 in Monocytes by Activating the 7-Transmembrane G-Protein–Coupled Receptor FPRL1/LXA4R

Because envelope gp120 of various strains of human immu-nodeficiency virus type 1 (HIV-1) downregulates the expres-sion and function of a variety of chemoattractant receptors through a process of heterologous desensitization, we inves-tigated whether epitopes derived from gp120 could mimic the effect. A synthetic peptide domain, designated F peptide, corresponding to amino acid residues 414-434 in the V4-C4 region of gp120 of the HIV-1 Bru strain, potently reduced monocyte binding and chemotaxis response to macrophage inflammatory protein 1b (MIP-1b) and stromal cell-derived factor 1a (SDF-1a), chemokines that use the receptors CCR5 and CXCR4, respectively. Further study showed that F pep-tide by itself is an inducer of chemotaxis and calcium mobilization in human monocytes and neutrophils. In cross-desensitization experiments, among the numerous chemoat