Abstract
To test the anti-human immunodeficiency virus type-1 (HIV-1) activity of 3,6,9,12-tetraazatetradecane-1,14-diylbis(zinc dithiocarbamate)-S,S'-dioxide (cyclic zinc-dithiocarbamate-S, S'-dioxide), MAGI and MAGIC-5 cells were used; the former express CXCR4 and the latter express both CXCR4 and CCR5, which are HIV-1 coreceptors. The compound markedly inhibited HIV-1 X4 (CXCR4-using) viral replication in both MAGI and MAGIC-5 cells. On the other hand, the replication of HIV-1 R5X4 (both CXCR4-and CCR5-using) in MAGI cells but not MAGIC-5 cells was inhibited by the compound. The compound was found to specifically inhibit HIV-1 (X4) envelope-mediated cell-to-cell fusion, binding of anti-CXCR4 monoclonal antibody (12G5) to CXCR4 expressed on the surface of cells, and calcium flux induced by stromal-derived factor-1alpha (SDF-1alpha) bound to CXCR4. The results suggest that the compound inhibited CXCR4-mediated HIV-1 infection by influencing to the HIV-1 coreceptor activity of CXCR4.
Copyright 2000 Academic Press.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antibodies, Monoclonal / immunology
-
Antibodies, Monoclonal / pharmacology
-
Calcium / metabolism
-
Cell Fusion / drug effects
-
Cell Line
-
Chemokine CCL5 / pharmacology
-
Chemokine CXCL12
-
Chemokines, CXC / antagonists & inhibitors
-
Chemokines, CXC / pharmacology
-
Cyclic S-Oxides / chemistry
-
Cyclic S-Oxides / pharmacology*
-
Cytopathogenic Effect, Viral / drug effects
-
DNA, Viral / analysis
-
DNA, Viral / genetics
-
Flow Cytometry
-
Giant Cells / drug effects
-
Giant Cells / metabolism
-
Giant Cells / pathology
-
Giant Cells / virology
-
HIV-1 / drug effects*
-
HIV-1 / genetics
-
HIV-1 / metabolism*
-
HIV-1 / physiology
-
Humans
-
Inhibitory Concentration 50
-
Organometallic Compounds / chemistry
-
Organometallic Compounds / pharmacology*
-
Proviruses / drug effects
-
Proviruses / genetics
-
Receptors, CCR5 / genetics
-
Receptors, CCR5 / immunology
-
Receptors, CCR5 / metabolism
-
Receptors, CXCR4 / antagonists & inhibitors*
-
Receptors, CXCR4 / genetics
-
Receptors, CXCR4 / immunology
-
Receptors, CXCR4 / metabolism*
Substances
-
3,6,9,12-tetraazatetradecane-1,14-diylbis(zinc dithiocarbamate)-S,S'-dioxide
-
Antibodies, Monoclonal
-
CXCL12 protein, human
-
Chemokine CCL5
-
Chemokine CXCL12
-
Chemokines, CXC
-
Cyclic S-Oxides
-
DNA, Viral
-
Organometallic Compounds
-
Receptors, CCR5
-
Receptors, CXCR4
-
Calcium