The Effect of Early HIV-1 Infection on Expression and Function of the Chemokine Receptor CXCR4

2000 ◽  
Vol 28 (1) ◽  
pp. A30-A30
Author(s):  
Brendan J. Murphy ◽  
Richard Q. Zheng ◽  
Keith E. Nye
Keyword(s):  
Chemokine Receptor ◽  
Chemokine Receptor Cxcr4 ◽  
And Function ◽  
Hiv 1

scholarly journals Structure and Function of CC-Chemokine Receptor 5 Homologues Derived from Representative Primate Species and Subspecies of the Taxonomic Suborders Prosimii and Anthropoidea

2003 ◽  
Vol 77 (22) ◽  
pp. 12310-12318 ◽  
Author(s):  
Kevin J. Kunstman ◽  
Bridget Puffer ◽  
Bette T. Korber ◽  
Carla Kuiken ◽  
Una R. Smith ◽  
...  
Keyword(s):  
Amino Acid ◽  
Chemokine Receptor ◽  
Transmembrane Domain ◽  
Structure And Function ◽  
Primate Species ◽  
Amino Acid Substitutions ◽  
Immunodeficiency Virus ◽  
And Function ◽  
Cc Chemokine Receptor 5 ◽  
Hiv 1

ABSTRACT A chemokine receptor from the seven-transmembrane-domain G-protein-coupled receptor superfamily is an essential coreceptor for the cellular entry of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) strains. To investigate nonhuman primate CC-chemokine receptor 5 (CCR5) homologue structure and function, we amplified CCR5 DNA sequences from peripheral blood cells obtained from 24 representative species and subspecies of the primate suborders Prosimii (family Lemuridae) and Anthropoidea (families Cebidae, Callitrichidae, Cercopithecidae, Hylobatidae, and Pongidae) by PCR with primers flanking the coding region of the gene. Full-length CCR5 was inserted into pCDNA3.1, and multiple clones were sequenced to permit discrimination of both alleles. Compared to the human CCR5 sequence, the CCR5 sequences of the Lemuridae, Cebidae, and Cercopithecidae shared 87, 91 to 92, and 96 to 99% amino acid sequence homology, respectively. Amino acid substitutions tended to cluster in the amino and carboxy termini, the first transmembrane domain, and the second extracellular loop, with a pattern of species-specific changes that characterized CCR5 homologues from primates within a given family. At variance with humans, all primate species examined from the suborder Anthropoidea had amino acid substitutions at positions 13 (N to D) and 129 (V to I); the former change is critical for CD4-independent binding of SIV to CCR5. Within the Cebidae, Cercopithecidae, and Pongidae (including humans), CCR5 nucleotide similarities were 95.2 to 97.4, 98.0 to 99.5, and 98.3 to 99.3%, respectively. Despite this low genetic diversity, the phylogeny of the selected primate CCR5 homologue sequences agrees with present primate systematics, apart from some intermingling of species of the Cebidae and Cercopithecidae. Constructed HOS.CD4 cell lines expressing the entire CCR5 homologue protein from each of the Anthropoidea species and subspecies were tested for their ability to support HIV-1 and SIV entry and membrane fusion. Other than that of Cercopithecus pygerythrus, all CCR5 homologues tested were able to support both SIV and HIV-1 entry. Our results suggest that the shared structure and function of primate CCR5 homologue proteins would not impede the movement of primate immunodeficiency viruses between species.

scholarly journals A Novel Synthetic Bivalent Ligand To Probe Chemokine Receptor CXCR4 Dimerization and Inhibit HIV-1 Entry

Biochemistry ◽  
2012 ◽  
Vol 51 (36) ◽  
pp. 7078-7086 ◽  
Author(s):  
Won-Tak Choi ◽  
Santhosh Kumar ◽  
Navid Madani ◽  
Xiaofeng Han ◽  
Shaomin Tian ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Bivalent Ligand ◽  
Chemokine Receptor Cxcr4 ◽  
Hiv 1

Butein downregulates chemokine receptor CXCR4 expression and function through suppression of NF-κB activation in breast and pancreatic tumor cells

2010 ◽  
Vol 80 (10) ◽  
pp. 1553-1562 ◽  
Author(s):  
Angeline Wei Ling Chua ◽  
Hui Sin Hay ◽  
Peramaiyan Rajendran ◽  
Muthu K. Shanmugam ◽  
Feng Li ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Chemokine Receptor ◽  
Pancreatic Tumor ◽  
Cxcr4 Expression ◽  
Chemokine Receptor Cxcr4 ◽  
And Function

HIV-1 gp120 enhances giant depolarizing potentials via chemokine receptor CXCR4 in neonatal rat hippocampus

2006 ◽  
Vol 23 (5) ◽  
pp. 1120-1128 ◽  
Author(s):  
Alexander Kasyanov ◽  
Hirokazu Tamamura ◽  
Nobutaka Fujii ◽  
Huangui Xiong
Keyword(s):  
Chemokine Receptor ◽  
Rat Hippocampus ◽  
Neonatal Rat ◽  
Chemokine Receptor Cxcr4 ◽  
Hiv 1

scholarly journals A Small-molecule Inhibitor Directed against the Chemokine Receptor CXCR4 Prevents its Use as an HIV-1 Coreceptor

1997 ◽  
Vol 186 (8) ◽  
pp. 1395-1400 ◽  
Author(s):  
Benjamin J. Doranz ◽  
Kathie Grovit-Ferbas ◽  
Matthew P. Sharron ◽  
Si-Hua Mao ◽  
Matthew Bidwell Goetz ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Small Molecule ◽  
Chemokine Receptor ◽  
Viral Entry ◽  
Small Molecule Inhibitor ◽  
Chemokine Receptor Cxcr4 ◽  
Mechanism Of Inhibition ◽  
Molecule Inhibitor ◽  
Immunodeficiency Virus ◽  
Hiv 1

The chemokine receptor CXCR4 is the major coreceptor used for cellular entry by T cell– tropic human immunodeficiency virus (HIV)-1 strains, whereas CCR5 is used by macrophage (M)-tropic strains. Here we show that a small-molecule inhibitor, ALX40-4C, inhibits HIV-1 envelope (Env)-mediated membrane fusion and viral entry directly at the level of coreceptor use. ALX40-4C inhibited HIV-1 use of the coreceptor CXCR4 by T- and dual-tropic HIV-1 strains, whereas use of CCR5 by M- and dual-tropic strains was not inhibited. Dual-tropic viruses capable of using both CXCR4 and CCR5 were inhibited by ALX40-4C only when cells expressed CXCR4 alone. ALX40-4C blocked stromal-derived factor (SDF)-1α–mediated activation of CXCR4 and binding of the monoclonal antibody 12G5 to cells expressing CXCR4. Overlap of the ALX40-4C binding site with that of 12G5 and SDF implicates direct blocking of Env interactions, rather than downregulation of receptor, as the mechanism of inhibition. Thus, ALX40-4C represents a small-molecule inhibitor of HIV-1 infection that acts directly against a chemokine receptor at the level of Env-mediated membrane fusion.

The implication of the chemokine receptor CXCR4 in HIV-1 envelope protein-induced apoptosis is independent of the G protein-mediated signalling

AIDS ◽  
1999 ◽  
Vol 13 (8) ◽  
pp. 909-917 ◽  
Author(s):  
Julià Blanco ◽  
Etienne Jacotot ◽  
Cecilia Cabrera ◽  
Ana Cardona ◽  
Bonaventura Clotet ◽  
...  
Keyword(s):  
G Protein ◽  
Chemokine Receptor ◽  
Envelope Protein ◽  
Chemokine Receptor Cxcr4 ◽  
Induced Apoptosis ◽  
Hiv 1

Synthesis and Structure−Activity Relationships of Phenylenebis(methylene)- Linked Bis-azamacrocycles That Inhibit HIV-1 and HIV-2 Replication by Antagonism of the Chemokine Receptor CXCR4

1999 ◽  
Vol 42 (19) ◽  
pp. 3971-3981 ◽  
Author(s):  
Gary J. Bridger ◽  
Renato T. Skerlj ◽  
Sreenivasan Padmanabhan ◽  
Stephen A. Martellucci ◽  
Geoffrey W. Henson ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Structure Activity Relationships ◽  
Chemokine Receptor Cxcr4 ◽  
Structure Activity ◽  
Hiv 1

scholarly journals Shared Usage of the Chemokine Receptor CXCR4 by Primary and Laboratory-Adapted Strains of Feline Immunodeficiency Virus

1999 ◽  
Vol 73 (5) ◽  
pp. 3661-3671 ◽  
Author(s):  
Jennifer Richardson ◽  
Gianfranco Pancino ◽  
Rastine Merat ◽  
Thierry Leste-Lasserre ◽  
Anne Moraillon ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Feline Immunodeficiency Virus ◽  
Type I ◽  
Dependent Manner ◽  
Amino Terminal ◽  
Species Origin ◽  
Chemokine Receptor Cxcr4 ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Strains of the feline immunodeficiency virus (FIV) presently under investigation exhibit distinct patterns of in vitro tropism. In particular, the adaptation of FIV for propagation in Crandell feline kidney (CrFK) cells results in the selection of strains capable of forming syncytia with cell lines of diverse species origin. The infection of CrFK cells by CrFK-adapted strains appears to require the chemokine receptor CXCR4 and is inhibited by its natural ligand, stromal cell-derived factor 1α (SDF-1α). Here we found that inhibitors of CXCR4-mediated infection by human immunodeficiency virus type I (HIV-1), such as the bicyclam AMD3100 and short peptides derived from the amino-terminal region of SDF-1α, also blocked infection of CrFK by FIV. Nevertheless, we observed differences in the ranking order of the peptides as inhibitors of FIV and HIV-1 and showed that such differences are related to the species origin of CXCR4 and not that of the viral envelope. These results suggest that, although the envelope glycoproteins of FIV and HIV-1 are substantially divergent, FIV and HIV-1 interact with CXCR4 in a highly similar manner. We have also addressed the role of CXCR4 in the life cycle of primary isolates of FIV. Various CXCR4 ligands inhibited infection of feline peripheral blood mononuclear cells (PBMC) by primary FIV isolates in a concentration-dependent manner. These ligands also blocked the viral transduction of feline PBMC by pseudotyped viral particles when infection was mediated by the envelope glycoprotein of a primary FIV isolate but not by the G protein of vesicular stomatitis virus, indicating that they act at an envelope-mediated step and presumably at viral entry. These findings strongly suggest that primary and CrFK-adapted strains of FIV, despite disparate in vitro tropisms, share usage of CXCR4.

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