Document Detail


T20/DP178, an ectodomain peptide of human immunodeficiency virus type 1 gp41, is an activator of human phagocyte N-formyl peptide receptor.
MedLine Citation:
PMID:  10339497     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Blood     Volume:  93     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  1999 Jun 
Date Detail:
Created Date:  1999-06-24     Completed Date:  1999-06-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3885-92     Citation Subset:  AIM; IM; X    
Affiliation:
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.
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MeSH Terms
Descriptor/Qualifier:
Cells, Cultured
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
Grant Support
ID/Acronym/Agency:
N01-CO-56000/CO/NCI NIH HHS
Chemical
Reg. No./Substance:
0/HIV Envelope Protein gp41; 0/Peptide Fragments; 0/Receptors, Formyl Peptide; 0/Receptors, Immunologic; 0/Receptors, Peptide; 0/peptide T20

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