T20/DP178, an ectodomain peptide of human immunodeficiency virus type 1 gp41, is an activator of human phagocyte N-formyl peptide receptor

Human immunodeficiency virus type 1 (HIV-1) envelope protein gp41 mediates viral fusion with human host cells. The peptide segment T20/DP178, located in the C-terminus of the ectodomain of gp41, interacts with the N-terminal leucine zipper-like domain on 9941 to establish the fusogenic conformation of the virus. Synthetic T20/DP178 peptide is highly efficacious in inhibiti ng HIV-1 infection in vitro by disrupting the transformation of fusogenic s tatus of viral gp41; thus, it has been proposed for clinical trial. We repo rt that synthetic T20/DP178 is a chemoattractant and activator of human per ipheral blood phagocytes but not of T lymphocytes. We further demonstrate t hat T20/DP178 specifically activates a seven-transmembrane, G-protein-coupl ed phagocyte receptor for N-formylated chemotactic peptides, formyl peptide receptor (FPR), Moreover, synthetic T20/DP178 analogs lacking N-terminal a mino acids acted as FPR antagonists. Our results suggest that gp41 peptides regulate phagocyte function via FPR and identify a novel mechanism by whic h HIV-1 may modulate innate immunity. (C) 1999 by The American Society of H ematology.