N36, a synthetic N-terminal heptad repeat domain of the HIV-1 envelope protein gp41, is an activator of human phagocytes.
Human immunodeficiency virus type 1 (HIV-1) envelope protein gp41 mediates viral fusion with human host cells. In this study we show that N36, a synthetic peptide derived from the N-terminus of gp41, induced directional migration and calcium mobilization in human monocytes and neutrophils. The activity of N36 on phagocytes was pertussis toxin sensitive, suggesting involvement of a Gi-coupled seven-transmembrane receptor(s). Since high concentrations of the bacterial chemotactic peptide fMet-Leu-Phe (fMLF) partially desensitized the calcium mobilizing activity of N36 in phagocytes, we postulated that N36 might use a low-affinity fMLF receptor. By using cells stably expressing fMLF receptor FPR or FPRL1, we demonstrate that N36 uses FPRL1 as a functional receptor. Our results suggest that HIV-1 gp41 may contain a fragment(s) that activates the innate host immune cells through FPRL1. Since the activation of FPRL1 in monocytes has been shown to heterologously desensitize chemokine receptors, the reduced phagocyte response to chemoattractants seen in AIDS patients may be attributed, at least in part, to heterologous desensitization.
Le
Y
Y
Laboratory of Molecular Immunoregulation, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland, 21702, USA.
Jiang
S
S
Hu
J
J
Gong
W
W
Su
S
S
Dunlop
N M
NM
Shen
W
W
Li
B
B
Ming Wang
J
J
D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009000:Monocytes / Q000166:cytology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010586:Phagocytes / Q000187:drug effects* / Q000502:physiology*; D017434:Protein Structure, Tertiary
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; C407148:peptide N36; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium