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.
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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.)
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Chemical References |
- HIV Envelope Protein gp41
- Peptide Fragments
- Receptors, Formyl Peptide
- Receptors, Immunologic
- Receptors, Peptide
- Enfuvirtide
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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
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