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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemokine stromal-cell-derived factor-1alpha (SDF-1alpha) chemoattracts lymphocytes and CD34+ haematopoietic progenitors and is the ligand for CXCR4 (CXC chemokine receptor 4), the main co-receptor for T-tropic HIV-1 strains. SDF-1alpha was NH2-terminally cleaved to SDF-1alpha(3-68) by dipeptidyl-peptidase IV (CD26/DPP IV), which is present in blood in soluble and membrane-bound form. SDF-1alpha(3-68) lost both lymphocyte chemotactic and CXCR4-signaling properties. However, SDF-1alpha(3-68) still desensitized the SDF-1alpha(1-68)-induced Ca2+ response. In contrast to CD26/DPP IV-processed RANTES(3-68), SDF-1alpha(3-68) had diminished potency to inhibit HIV-1 infection. Thus, CD26/DPP IV impairs the inflammatory and haematopoietic potency of chemokines but plays a dual role in AIDS.
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PMID:Processing by CD26/dipeptidyl-peptidase IV reduces the chemotactic and anti-HIV-1 activity of stromal-cell-derived factor-1alpha. 971 Feb 54

In this cross-sectional study, 53 cervicovaginal lavage samples (CVL) from 41 women were analyzed for the chemokines interleukin-8 (IL-8), regulated-on-activation normal T-expressed and secreted (RANTES) factor, and macrophage inflammatory protein-1alpha (MIP-1alpha) by enzyme-linked immunosorbent assay (ELISA). IL-8 was detected in 81% of CVL, whereas RANTES was detected in 32%, and MIP-1alpha in 15% of the CVL. The mean levels of IL-8, RANTES, and MIP-1alpha in positive samples were 396 pg/ml, 102 pg/ml, and 34 pg/ml, respectively. IL-8 levels correlated positively with IL-1beta and IgG in a subset of CVL samples. RANTES levels correlated positively with complement protein levels. Additionally, the levels of RANTES, but not MIP-1alpha, reached levels reported in previous studies of the effects of beta chemokines to inhibit HIV replication. These results suggest that measuring chemokines in CVL specimens can provide important information regarding immune responses in the genital tract.
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PMID:Chemokines are present in the genital tract of HIV-seropositive and HIV-seronegative women: correlation with other immune mediators. 971 41

We have developed a genetic "intrakine" strategy to inactivate the CC-chemokine receptor 5 (CCR-5), the principal coreceptor for macrophage (M)-tropic HIV-1 viruses (Yang et al, 1997). The inactivation of CCR5 was achieved by targeting a modified CC-chemokine (RANTES) to the lumen of the endoplasmic reticulum (ER) to block the transport of the newly synthesized CCR-5. The transduced lymphocytes with the phenotypic CCR5 knockout were shown to be resistant to M-tropic HIV-1 infection. This study illustrated the feasibility of the intrakine strategy to block HIV-1 infection. In our current study, the potential clinical application of the intrakine approach was further evaluated in human peripheral blood lymphocytes (PBLs). PBLs were transduced with the RANTES intrakine gene by using retroviral vectors with the truncated low-affinity human nerve growth factor receptor (deltaNGFR) marker, and then isolated by an anti-NGFR antibody/magnetic bead method. The surface expression of CCR-5 in the transduced lymphocytes was dramatically inhibited, as demonstrated by flow cytometric assays. The transduced PBLs were shown to resist various types of M-tropic HIV-1 virus infection. The cell viability, cell proliferation rates, and cell surface markers of the intrakine-transduced PBLs were shown to be comparable to those of control PBLs. The transduced PBLs were also found to respond to the stimulation of various CXC- and CC-chemokines, other than RANTES. The transduced PBLs responded to tetanus antigen stimulation by increasing IL-2 production and cell proliferation. In addition, a functionally defective mutant of RANTES that retains its binding activity to CCR-5, but loses its signaling ability, was used to generate a mutant RANTES intrakine. The primary lymphocytes transduced with the mutant RANTES intrakine were found to be resistant to M-tropic HIV-1 infection. From these results, we conclude that the primary human lymphocytes transduced with either the wild-type or functionally defective RANTES intrakine are resistant to M-tropic HIV-1 infection, and maintain their basic biological functions. This study, therefore, indicates the potential clinical application of the intrakine approach for HIV-1 gene therapy.
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PMID:Anti-HIV type 1 activity of wild-type and functional defective RANTES intrakine in primary human lymphocytes. 975 28

The beta-chemokine RANTES (regulated on activation, normal T cell expressed and secreted) suppresses the infection of susceptible host cells by macrophage tropic strains of HIV-1. This effect is attributed to interactions of this chemokine with a 7-transmembrane domain receptor, CCR5, that is required for virus-cell fusion and entry. Here we identify domains of RANTES that contribute to its biological activities through structure-function studies using a new monoclonal antibody, mAb 4A12, isolated from mice immunized with recombinant human RANTES. This monoclonal antibody (mAb) blocked the antiviral activity of RANTES in infectivity assays with HIV-1Bal, and inhibited the mobilization of intracellular Ca2+ elicited by RANTES, yet recognized this chemokine bound to cell surfaces. Epitope mapping using limited proteolysis, reversed phase high-performance liquid chromatography, and mass spectrometry suggest that residues 55-66 of RANTES, which include the COOH-terminal alpha-helical region implicated as the glycosaminoglycan (GAG) binding domain, overlap the determinant recognized by mAb 4A12. This is supported by affinity chromatography studies, which showed that RANTES could be eluted specifically by heparin from a mAb 4A12 immunoaffinity matrix. Removal of cell surface GAGs by enzymatic digestion greatly reduced the ability of mAb 4A12 to detect RANTES passively bound on cell surfaces and abrogated the ability of RANTES to elicit an intracellular Ca2+ signal. Taken together, these studies demonstrate that the COOH-terminal alpha-helical region of RANTES plays a key role in GAG-binding, antiviral activity, and intracellular Ca2+ signaling and support a model in which GAGs play a key role in the biological activities of this chemokine.
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PMID:A new monoclonal antibody, mAb 4A12, identifies a role for the glycosaminoglycan (GAG) binding domain of RANTES in the antiviral effect against HIV-1 and intracellular Ca2+ signaling. 981 69

The natural CC-chemokine RANTES(3-68), missing two NH2-terminal residues, has been isolated from leukocytes and tumor cells. The highly specific aminopeptidase dipeptidyl peptidase IV (DPP IV), also called CD26, was shown to be responsible for this NH2-terminal truncation of RANTES. Here it is reported that CD26/DPP IV treatment of RANTES enhances its anti-HIV-1 activity. RANTES(3-68) inhibited infection of PBMC by M-tropic HIV-1 strains ten-fold more efficiently than intact RANTES. This difference in antiviral potency between intact and truncated RANTES was even more pronounced (at least 25-fold) in CCR5-transfected cell lines. In HOS.CD4.CCR5 transfected cells, RANTES(1-68) had virtually no anti-HIV-1 activity (IC50 > 130 nM), whereas RANTES(3-68) was a potent inhibitor of HIV-1 replication (1C50: 5.5 nM). The anti-HIV-1 activity of RANTES(1-68) in the different cell types correlated with the expression of CD26. Moreover, the addition of soluble CD26 together with RANTES(1-68) significantly enhanced the antiviral activity of RANTES in HOS.CD4.CCR5 cells (IC50: 13 nM). These observations point to an important role of CD26-mediated processing of RANTES in inhibiting the replication of CCR5-binding HIV strains in HIV-infected persons and in preventing the development of AIDS.
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PMID:CD26-processed RANTES(3-68), but not intact RANTES, has potent anti-HIV-1 activity. 983 58

We have studied the effects of CC-chemokines on human immunodeficiency virus type 1 (HIV-1) infection, focusing on the infectivity enhancement caused by RANTES. High RANTES concentrations increase the infectivity of HIV-1 isolates that use CXC-chemokine receptor 4 for entry. However, RANTES can have a similar enhancing effect on macrophagetropic viruses that enter via CC-chemokine receptor 5 (CCR5), despite binding to the same receptor as the virus. Furthermore, RANTES enhances the infectivity of HIV-1 pseudotyped with the envelope glycoprotein of murine leukemia virus or vesicular stomatitis virus, showing that the mechanism of enhancement is independent of the route of virus-cell fusion. The enhancing effects of RANTES are not mediated via CCR5 or other known chemokine receptors and are not mimicked by MIP-1alpha or MIP-1beta. The N-terminally modified derivative aminooxypentane RANTES (AOP-RANTES) efficiently inhibits HIV-1 infection via CCR5 but otherwise mimics RANTES by enhancing viral infectivity. There are two mechanisms of enhancement: one apparent when target cells are pretreated with RANTES (or AOP-RANTES) for several hours, and the other apparent when RANTES (or AOP-RANTES) is added during virus-cell absorption. We believe that the first mechanism is related to cellular activation by RANTES, whereas the second is an increase in virion attachment to target cells.
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PMID:Enhancement of human immunodeficiency virus type 1 infection by the CC-chemokine RANTES is independent of the mechanism of virus-cell fusion. 984 74

The Duffy Antigen Receptor for Chemokines (DARC) belongs to a family of erythrocyte chemokine receptors that bind C-X-C and C-C chemokines such as interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1) and regulated-on-activation, normal T cell-expressed and -secreted (RANTES), but not macrophage inflammatory protein 1 alpha (MIP-1 alpha) or MIP-1 beta. DARC has also been identified to a receptor for malaria parasites Plasmodium vivax and Plasmodium knowlesi. In the present study, we show that HIV-1 binds to RBCs from Caucasian individuals via DARC making RBCs able to transmit HIV to peripheral blood mononuclear cells (PBMCs). Furthermore, binding of HIV-1 particles to RBCs is inhibited by treating these cells with recombinant RANTES, but not with recombinant MIP-1 alpha prior to their incubation with HIV-1. This finding suggests that RBCs may function as a reservoir for HIV-1 or as a receptor for the entry of HIV-1 into CD4-cell subsets as well as neurons or endothelial cells.
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PMID:Binding of HIV-1 to RBCs involves the Duffy antigen receptors for chemokines (DARC). 992 12

The effect of beta chemokines on human immunodeficiency virus type 1 (HIV-1) infection of primary macrophages is controversial, and their effect on HIV-2 infection of these cells has not yet been documented. We examined the effect of synthetic and recombinant regulated-on-activation, normal T cell-expressed and -secreted (RANTES) on HIV-1 and HIV-2 infection of primary monocyte-derived-macrophages (MDM) that were obtained as the adherent cells of 5-day cultures of blood mononuclear cells (PBMC), followed by 2-day culture without peripheral blood mononuclear cells (PBMCs) nor added cytokines. These MDM expressed CD4, CCR5 and CXCR4, the major coreceptors for HIV macrophage- and T cell-tropic isolates, respectively. Infection of MDM from different donors with HIV-1 or HIV-2 macrophage-tropic strains was reproducibly inhibited by RANTES. This inhibition depended on RANTES continuous presence in culture during and after infection. Treatment of MDM with RANTES just before or during, but not after, exposure to virus did not protect MDM from infection. When RANTES was added after MDM had been infected, and was continuously maintained in culture thereafter, no inhibition occurred and limited enhancement of infection could be observed. These data indicate that RANTES inhibits HIV-1 as well as HIV-2 infection of MDM, likely at a post-binding step, and support the role of CCR5 as the major coreceptor for HIV-1 and HIV-2 entry into primary macrophages.
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PMID:Effect of RANTES on the infection of monocyte-derived primary macrophages by human immunodeficiency virus type 1 and type 2. 992 14

The CC-chemokine receptor 5 (CCR5) mediates activation of T lymphocytes and macrophages by chemokines and is a major co-receptor for macrophage-tropic HIV-1 strains. Recently, it was shown that the natural CCR5 ligands RANTES, macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and amino-terminal modifications of RANTES (Met-RANTES, AOP-RANTES) significantly differ in their abilities to induce sequestration of CCR5 from cellular surfaces. It was hypothesized that these findings may account for the observed differences between these molecules to inhibit HIV infectivity in vitro. Herein we review our work on early regulatory mechanisms that are initiated by ligand binding to CCR5 and that, conceptually, are involved in receptor endocytosis. A better understanding of these mechanisms may provide new therapeutic strategies to prevent HIV infection.
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PMID:Chemokine-induced phosphorylation of CC chemokine receptor 5 (CCR5). 1008 May 28

Alveolar macrophages (AM) are important host-defense cells and targets of human immunodeficiency virus type 1 (HIV-1) infection. However, the receptors mediating HIV-1 entry into AM are not completely characterized. We observed that, in addition to CD4 receptors, AM from healthy adults expressed low levels of CCR5, CCR3, and CXCR4 chemokine receptors by flow cytometry, and specific messenger RNA was detected for all three receptors by reverse transcriptase/polymerase chain reaction. The macrophage monocytotropic (M-tropic; YU2) and dual-tropic (89.6) HIV-1 env-pseudotypes entered AM efficiently, as expected given CCR3 and CCR5 expression. However, the T-lymphocytotropic (T-tropic; HXB2) pseudotype did not enter AM despite expression of the appropriate chemokine coreceptor CXCR4. Incubation of AM with regulated on activation, normal T cells expressed and secreted (RANTES) significantly impaired entry of the M-tropic (YU2) HIV-1 pseudotype, whereas SDF-1beta or eotaxin did not impair entry. The entry of simian immunodeficiency virus (SIV) pbj1.9 env-pseudotype into AM was not blocked by RANTES, SDF-1beta, or eotaxin. The competence of these chemokine receptors for virus entry was confirmed in Cf2Th canine thymocytes cotransfected with the human CD4 and chemokine receptors. Entry of the M-tropic (YU2) HIV-1 pseudotype was shown to be mediated by either CCR3 or CCR5, the T-tropic (HXB2) HIV-1 pseudotype by CXCR4, and the dual-tropic (89.6) HIV-1 or the SIVpbj1. 9 pseudotype by CCR5, CCR3, or CXCR4. Our data indicate that the mechanisms for HIV-1 entry are both receptor-specific and cell type-specific, and that chemokine receptor expression on AM does not fully explain cell susceptibility to different virus isolates.
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PMID:CD4 receptor-dependent entry of human immunodeficiency virus type-1 env-pseudotypes into CCR5-, CCR3-, and CXCR4-expressing human alveolar macrophages is preferentially mediated by the CCR5 coreceptor. 1022 56


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