Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10930185 | Cytokine & Growth Factor Reviews | 2005 | 19 Pages |
Abstract
The chemokine receptors CXCR4 and CCR5 are the main coreceptors used by the T-cell-tropic (CXCR4-using, X4) and macrophage-tropic (CCR5-using, R5) HIV-1 strains, respectively, for entering their CD4+ target cells. In this review, we focus on the function of these chemokine receptors in HIV infection and their role as novel targets for viral inhibition. Besides some modified chemokines with antiviral activity, several low-molecular weight CCR5 and CXCR4 antagonistic compounds have been described with potent antiviral activity. The best CXCR4 antagonists described are the bicyclam derivatives, which consistently block X4 but also R5/X4 viral replication in PBMCs. We believe that chemokine receptor antagonists will become important new antiviral drugs to combat AIDS. Both CXCR4 and CCR5 chemokine receptor inhibitors will be needed in combination and even in combinations of antiviral drugs that also target other aspects of the HIV replication cycle to obtain optimum antiviral therapeutic effects.
Keywords
LTRIP3MDCGPCRCXCR4GRKPDIGCPRPSDC-SIGNCCR5NRTIsNNRTIsFLIPRPIP2granulocyte chemotactic proteinFDAregulated on activation normal T-cell expressed and secretedsyncytium-inducingnon-syncytium-inducingHAARTPI3KMCPGTPMIPAOPGFPSDF-1NSIG protein-coupled receptor kinaseMAPKAntagonistAIDSlong-term nonprogressorsLong terminal repeatClinical isolatehighly active antiretroviral therapyFood and Drug AdministrationDendritic cellacquired immune deficiency syndromestromal cell-derived factor-1transmembranephosphatidylinositol 4,5-biphosphatephosphoinositide 3 kinaseFLuorometric Imaging Plate Readerm/mRANTESNucleoside reverse transcriptase inhibitorsNon-Nucleoside Reverse Transcriptase InhibitorsMonocytes/macrophagesHIVhuman immunodeficiency virusmacrophage inflammatory proteinprotein-disulfide isomerasemonocyte chemoattractant proteingreen fluorescent proteinmitogen activated protein kinaseGlycoproteinGuanosine triphosphatechemokine receptorG protein-coupled receptor
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Authors
Katrien Princen, Dominique Schols,