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...family function as coreceptors with the primary receptor CD4 to allow entry of various strains of human immunodeficiency virus type 1 (HIV-1) into the cells [5-8]. T-cell-tropic X4 HIV-1 use CD4 and chemokine receptor CXCR4 for entry into target cells, whereas macrophage-tropic R5 HIV-1 use CD4 and chemokine receptor CCR5. Dual-tropic strains can use either CCR5 and CXCR4 as co-receptors. In addition, CCR3, CCR2, CXCR6 (Bonzo/STLR6) among other chemokine receptors can function as coreceptors and... Show Full Excerpts
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Down-regulation of cell surface CXCR4 by HIV-1
Choi, B., Gatti, P., Fermin, C., Vigh, S., Haislip, A., Garry, R. (2008) Virology Journal.
ABSTRACT
Expression of chemokine receptor CXCR4 in esophageal squamous cell and adenocarcinoma
Gockel, I., Schimanski, C., Heinrich, C., Wehler, T., Frerichs, K., Drescher, D., von Langsdorff, C., Domeyer, M., Biesterfeld, S., Galle, P., Junginger, T., Moehler, M. (2006) BMC Cancer.
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...]. Chemokines are a family of chemoattractant proteins that are classified depending on the arrangement of amino acids adjacent to conserved cysteine residues. CXCR4 is a seven-transmembrane G protein-coupled receptor and is also known as a coreceptor for HIV. SDF-1α (stem cell derived factor α), the natural ligand for CXCR4, is a member of the CXC chemokine family that has chemotactic activity for hematopoietic progenitor cells [7-10]. Thus far,... Show Full Excerpts 
Differential control of CXCR4 and CD4 downregulation by HIV-1 Gag
Valiathan, R., Resh, M. (2008) Virology Journal.
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...exhibit higher levels of activated MAP Kinase. These findings indicate that HIV-1 Gag impinges upon the normal function of cellular ESCRT complexes during EGFR downregulation. In order to determine whether downregulation of other receptors is sensitive to HIV-1 Gag expression, we have now investigated the kinetics of lysosomal downregulation of CD4 and CXCR4, in the presence and absence of Gag. CD4 and CXCR4 function as the receptor and co-receptor respectively for the entry of HIV-1... Show Full Excerpts 
Stromal Derived Factor-1 (SDF-1/CXCL12) and CXCR4 in renal cell carcinoma metastasis
Pan, J., Mestas, J., Burdick, M., Phillips, R., Thomas, G., Reckamp, K., Belperio, J., Strieter, R. (2006) Molecular Cancer.
ABSTRACT
Renal cell carcinoma (RCC) is characterized by organ-specific metastases. The chemokine stromal derived factor-1 (SDF-1/CXCL12) and its receptor CXCR4 have been suggested to regulate organ-specific metastasis in various other cancers. On this basis, we hypothesized that the biological axis of CXCL12 via interaction with its receptor, CXCR4, is a major mechanism for RCC metastasis. We demonstrated that CXCR4 was significantly expressed on circulating cytokeratin+ RCC cells from patients with known metastatic RCC. We detected up-regulation of CXCR4 mRNA and protein levels on a human RCC cell line by either knockdown of the von Hippel-Lindau (VHL) tumor suppressor... Show Full AbstractFULL-TEXT EXCERPTS
...inflammation [9-13]. Different cancers are found to express several chemokine receptors, and their corresponding ligands are expressed at sites of tumor metastases [6,7,14,15]. However, CXCR4 appears to be the major chemokine receptor expressed on cancer cells [4,5,8]. CXCR4 was originally discovered as the co-receptor for lymphotropic strains of HIV [16] and CXCL12 (stromal derived factor-1, SDF-1) is its lone ligand [17]. CXCL12 has been found to be secreted by bone marrow stromal cells and is... Show Full Excerpts 
Expression of chemokine receptor CXCR4 in nasopharyngeal carcinoma: pattern of expression and correlation with clinical outcome
Wang, N., Wu, Q., Fang, Y., Mai, H., Zeng, M., Shen, G., Hou, J., Zeng, Y. (2005) Journal of Translational Medicine.
ABSTRACT
Nasopharyngeal carcinoma (NPC) is a tumor derived from epithelial cells and Epstein-Barr virus infection has been reported to be a cause of this disease. Chemokine receptor CXCR4 was found to be involved in HIV infection and was highly expressed in human malignant breast tumors and the ligand for CXCR4, CXCL12 (SDF-1), exhibited high expression in organs in which breast cancer metastases are often found. The metastatic pattern of NPC is quite similar to that of malignant breast tumors. In this study, we investigated the expression of CXCR4 in nasopharyngeal carcinoma (NPC) tissues by immunohistostaining. We found different staining... Show Full AbstractFULL-TEXT EXCERPTS
...CXCR4 and CCR7 were highly expressed in human malignant breast tumors compared to normal breast tissue. The ligands for these receptors – CXCL12 (SDF-1) for CXCR4 and CCL21 for CCR7 – exhibit high expression in organs in which breast cancer metastases are often found. The organ tropism of metastatic NPC often recapitulates that observed in malignant breast tumors. In addition, Staller et al [6] observed an inverse correlation between CXCR4 expression and survival in... Show Full Excerpts 
Establishment of a novel CCR5 and CXCR4 expressing CD4+ cell line which is highly sensitive to HIV and suitable for high-throughput evaluation of CCR5 and CXCR4 antagonists
Princen, K., Hatse, S., Vermeire, K., De Clercq, E., Schols, D. (2004) Retrovirology.
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...Background After binding to the cellular CD4 receptor, HIV needs to bind one of the chemokine receptors CCR5 and CXCR4 to actually infect its target cells. CCR5 is the main coreceptor for R5 (M-tropic) viruses that are mainly isolated from patients in the early (asymptomatic) stage of HIV-infection. The more pathogenic X4 viruses that use CXCR4 as their major coreceptor often emerge in HIV-infected persons in a later stage of disease progression towards AIDS [1-4].... Show Full Excerpts 
HIV-1 resistance conferred by siRNA cosuppression of CXCR4 and CCR5 coreceptors by a bispecific lentiviral vector
Anderson, J., Akkina, R. (2005) AIDS Research and Therapy.
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...will be lower. Down regulation of the primary cell surface receptor CD4 and consequent inhibition of HIV-1 infection was shown using synthetic siRNAs. However, since CD4 is an essential cell surface molecule for immunological function, it is not a practical target for HIV gene therapy. Chemokine receptors CCR5 and CXCR4 play critical roles as coreceptors for viral entry during infection......deletion in the CCR5 gene results in the loss of this coreceptor thus conferring significant... Show Full Excerpts
The chemokine Sdf-1 and its receptor Cxcr4 are required for formation of muscle in zebrafish
Chong, S., Nguyet, L., Jiang, Y., Korzh, V. (2007) BMC Developmental Biology.
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...receptor CXCR4 [27,28] is used by HIV-1 for binding to the cell membrane [27,29-31]. SDF-1α [chemokine (C-X-C motif) ligand 12; zebrafish gene nomenclature committee] and its receptor CXCR4 [chemokine (C-X-C motif) receptor 4; zebrafish gene nomenclature committee] bind only each other [32-35]. Importantly, a study of the expression of SDF-1α/CXCR4 in the mouse embryo demonstrated expression of CXCR4......in zebrafish [43-47]. Our previous study demonstrated that the... Show Full Excerpts
CXCR4 expression in papillary thyroid carcinoma: induction by nitric oxide and correlation with lymph node metastasis
Yasuoka, H., Kodama, R., Hirokawa, M., Takamura, Y., Miyauchi, A., Sanke, T., Nakamura, Y. (2008) BMC Cancer.
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...(CXCR4), and that CXCR4 plays a critical role in homing of cancer cells to specific metastatic sites[6]. The CXCR4 ligand CXCL12 was found to be expressed in liver, bone marrow, lung, and lymph nodes. Furthermore, metastasis of cancer cells to regional lymph nodes and lung in immunodeficient mice were inhibited by a neutralizing antibody against CXCR4 [6]. However, how CXCR4 expression is regulated is largely unknown. We considered the possibility that the... Show Full Excerpts 
Fluorescence Resonance Energy Transfer Imaging Reveals that Chemokine-Binding Modulates Heterodimers of CXCR4 and CCR5 Receptors
Isik, N., Hereld, D., Jin, T. (2008) PLoS ONE.
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...oligomers [8], [9]. CXCR4 and CCR5 receptors regulate leukocyte chemotaxis in inflammation and also serve in conjunction with CD4 as co-receptors for HIV entry [1], [3]. CXCR4 normally functions as the receptor for the chemokine CXCL12/SDF-1, whereas CCR5 mediates responses to several chemokines, including CCL3/MIP1-α, CCL4/MIP1-β and CCL5/RANTES [2]. CXCR4 and CCR5 are co-expressed in several leukocyte populations including lymphocyte and monocytes [3], [10]. In addition to their... Show Full Excerpts 
Stable gene transfer of CCR5 and CXCR4 siRNAs by sleeping beauty transposon system to confer HIV-1 resistance
Tamhane, M., Akkina, R. (2008) AIDS Research and Therapy.
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...infection and replication, the cell surface coreceptors CCR5 and CXCR4 are essential for viral entry by macrophage tropic R5 and T-cell tropic-X4 HIV respectively [16,17]. The primary HIV infection is established by R5 virus and during the later stages of disease, T-cell tropic X4 virus predominates [17,18]. In nature, a segment of the human population containing a 32-base pair deletion in the CCR5......in effective viral inhibition. However, retroviral derived vectors were used in these... Show Full Excerpts
CXCR4 and CCR5 shRNA transgenic CD34+ cell derived macrophages are functionally normal and resist HIV-1 infection
Anderson, J., Akkina, R. (2005) Retrovirology.
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...]. A number of studies using siRNAs have targeted HIV genes as well as the cellular molecules critical for HIV entry, namely CD4, CXCR4 and CCR5 [18,19,21,23,24,33-37]. SiRNAs targeting HIV genes alone will not be sufficient to ward off chronic infection due to the high possibility of generating escape mutants [38,39]. Therefore by targeting host cellular genes critical for viral entry and/or replication, a more sustained efficacy of antiviral effects may be obtained. As a critical... Show Full Excerpts 
The Novel CXCL12γ Isoform Encodes an Unstructured Cationic Domain Which Regulates Bioactivity and Interaction with Both Glycosaminoglycans and CXCR4
Laguri, C., Sadir, R., Rueda, P., Baleux, F., Gans, P., Arenzana-Seisdedos, F., Lortat-Jacob, H. (2007) PLoS ONE.
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...are mediated by the G-protein coupled receptor CXCR4, to which the chemokine binds and triggers cell signaling [6], [12]. In addition to these physiological functions, CXCL12 is a potent inhibitor of the cellular entry of CXCR4-dependent human immunodeficiency virus [12]. Recently, we have documented that CXCR7 (RDC-1), also binds to- and is activated by- CXCL12 [13], although the biological role......]. CXCL12α binding to HS critically involves amino acids... Show Full Excerpts
Control of cell migration in the development of the posterior lateral line: antagonistic interactions between the chemokine receptors CXCR4 and CXCR7/RDC1
Dambly-Chaudière, C., Cubedo, N., Ghysen, A. (2007) BMC Developmental Biology.
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..., the chemokine receptor CXCR4 [11,12]. One of the two genes coding for this receptor, cxcr4b, is expressed in the migrating cells and is down-regulated in the cells at the trailing edge of the primordium [7]. The inactivation of sdf1a in morphant embryos, or of cxcr4b in mutant or morphant embryos, results in an arrest of migration [11,12]. A similar effect of cxcr4b inactivation has been observed......of the fish and human CXCR4 receptors... Show Full Excerpts
Infection of cells expressing CXCR4 mutants lacking N-glycosylation at the N-terminal extracellular domain is enhanced for R5X4-dualtropic human immunodeficiency virus type-1
Thordsen, I., Polzer, S., Schreiber, M. (2002) BMC Infectious Diseases.
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...Background The chemokine receptor CXCR4 belongs to the seven-transmembrane-domain G-protein-coupled receptor family and is one of the major coreceptors for human immunodeficiency virus type 1 (HIV-1) [1,2]. The trimolecular interaction between the HIV-1 receptor CD4, CXCR4 and viral envelope proteins (gp120/gp41) is the first step in HIV entry. Binding of gp120 to CD4 triggers conformational changes responsible for binding to the coreceptor. Binding to coreceptor is followed by further conformational changes in the gp41 subunit... Show Full Excerpts 
In vitro characterization and inhibition of the CXCR4/CXCL12 chemokine axis in human uveal melanoma cell lines
Di Cesare, S., Marshall, J., Fernandes, B., Logan, P., Antecka, E., Filho, V., Burnier, M. (2007) Cancer Cell International.
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...]. It is widely believed that the CXCR4/CXCL12 axis may play a critical role in guiding circulating malignant cells (CXCR4+ cells) to organ specific locations that actively secrete CXCL12 (SDF-1) such as bone, brain, liver, and lungs [10]. Many animal models have also shown very impressive results, while inhibiting the CXCR4/CXCL12 axis, significantly inhibiting and delaying the metastatic process [11,12]. It has also been recently established that high CXCR4... Show Full Excerpts 
A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction
Willett, B., McMonagle, E., Logan, N., Samman, A., Hosie, M. (2008) Retrovirology.
ABSTRACT
Feline immunodeficiency virus (FIV) targets helper T cells by attachment of the envelope glycoprotein (Env) to CD134, a subsequent interaction with CXCR4 then facilitating the process of viral entry. As the CXCR4 binding site is not exposed until CD134-binding has occurred then the virus is protected from neutralising antibodies targeting the CXCR4-binding site on Env. Prototypic FIV vaccines based on the FL4 strain of FIV contain a cell culture-adapted strain of FIV Petaluma, a CD134-independent strain of FIV that interacts directly with CXCR4. In addition to a characteristic increase in... Show Full AbstractFULL-TEXT EXCERPTS
...site for the coreceptor, usually the chemokine receptors CXCR4 and CCR5 [3,4]. Engagement of the coreceptor triggers a further conformational change in the Env complex that results in exposure of the gp41 fusion domain and initiates the process of fusion of the viral and cellular membranes. Given that the virus-receptor interaction initiates the process of viral entry, the binding sites on gp120......strains of FIV tested to date, utilise CD134 as a receptor for viral... Show Full Excerpts
Expression pattern of CXC chemokine receptor-4 is correlated with lymph node metastasis in human invasive ductal carcinoma
Kato, M., Kitayama, J., Kazama, S., Nagawa, H. (2003) Breast Cancer Research.
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...]. They showed that CXCR4 is highly expressed in malignant breast cancer but not in normal breast tissue, and the ligand SDF-1 was highly expressed in bone marrow, lung and lymph nodes, where breast cancer cells metastasize preferentially. Moreover, they demonstrated that neutralization with a specific monoclonal antibody against CXCR4 effectively inhibited the metastasis of breast cancer cells to the lung......tissues [12,13]. However, the immunostaining pattern of CXCR4 in various cancer tissues... Show Full Excerpts
Cultured Kaposi's sarcoma tumor cells exhibit a chemokine receptor repertoire that does not allow infection by HIV-1
Simonart, T., Debussher, C., Liesnard, C., Debaisieux, L., Delforge, M., de Lavareille, A., Hermans, P., Van Vooren, J., Stordeur, P. (2001) BMC Dermatology.
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...not harbor the CD4 antigen [9, 13, 14]. However, it is noteworthy that many cell types that do not express CD4, like endothelial cells, are also infectible to various strains of HIV-1 [15]. Cellular entry of HIV is now known to require one of several seven-transmembrane domain G-protein-coupled receptors, principally CXCR4, an α-chemokine receptor, and CCR5 whose natural ligands are β-chemokines [16, 17......, penicillin (100 U/ml) and streptomycin (100 μg/ml). No exogenous growth factor... Show Full Excerpts
Expression of HIV receptors, alternate receptors and co-receptors on tonsillar epithelium: implications for HIV binding and primary oral infection
Kumar, R., Maher, D., Herzberg, M., Southern, P. (2006) Virology Journal.
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...was established between HIV infection and virus recognition of co-receptors expressed on the target cell surface. The principal co-receptors, CCR5 and CXCR4, like the CD4 primary HIV receptor, are normal T cell surface proteins with key roles in immune signaling and T cell function, as reviewed in Berger et al. [30]. Epithelial cells that are susceptible to HIV infection have been reported to express CXCR4 and CCR5 [31,32] but other studies have not succeeded in... Show Full Excerpts