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

Abstract

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 gp41 to establish the fusogenic conformation of the virus. Synthetic T20/DP178 peptide is highly efficacious in inhibiting HIV-1 infection in vitro by disrupting the transformation of fusogenic status of viral gp41; thus, it has been proposed for clinical trial. We report that synthetic T20/DP178 is a chemoattractant and activator of human peripheral blood phagocytes but not of T lymphocytes. We further demonstrate that T20/DP178 specifically activates a seven-transmembrane, G-protein-coupled phagocyte receptor for N-formylated chemotactic peptides, formyl peptide receptor (FPR). Moreover, synthetic T20/DP178 analogs lacking N-terminal amino acids acted as FPR antagonists. Our results suggest that gp41 peptides regulate phagocyte function via FPR and identify a novel mechanism by which HIV-1 may modulate innate immunity.

• Authors: S B Su, W H Gong, J L Gao, W P Shen, M C Grimm, X Deng, P M Murphy, J J Oppenheim, J M Wang
• Journal: Blood (Blood) Vol. 93 Issue 11 Pg. 3885-92 (Jun 01 1999) ISSN: 0006-4971 [Print] United States
• PMID: 10339497 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• HIV Envelope Protein gp41
• Peptide Fragments
• Receptors, Formyl Peptide
• Receptors, Immunologic
• Receptors, Peptide
• Enfuvirtide

Topics

• Cells, Cultured
• Enfuvirtide
• HIV Envelope Protein gp41 (metabolism, pharmacology)
• HIV Infections (virology)
• HIV-1 (physiology)
• Humans
• Monocytes (physiology, virology)
• Neutrophils (physiology, virology)
• Peptide Fragments (metabolism, pharmacology)
• Phagocytosis (drug effects)
• Receptors, Formyl Peptide
• Receptors, Immunologic (physiology)
• Receptors, Peptide (physiology)
• Virus Replication