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 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.
Su
S B
SB
Laboratory of Molecular Immunoregulation, Division of Basic Sciences, and Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD, USA.
Gong
W H
WH
Gao
J L
JL
Shen
W P
WP
Grimm
M C
MC
Deng
X
X
Murphy
P M
PM
Oppenheim
J J
JJ
Wang
J M
JM
D002478:Cells, Cultured; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000378:metabolism* / Q000494:pharmacology; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D009000:Monocytes / Q000502:physiology* / Q000821:virology*; D009504:Neutrophils / Q000502:physiology* / Q000821:virology*; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000502:physiology*; D018000:Receptors, Peptide / Q000502:physiology*; D014779:Virus Replication
D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D000077560:Enfuvirtide