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

Leukocyte chemoattractants act through a rapidly growing subfamily of G protein-coupled receptors. We report the cloning of a novel human gene encoding an orphan receptor (ChemR23) related to the C3a, C5a and formyl Met-Leu-Phe receptors, and more distantly to the subfamilies of chemokine receptors. ChemR23 transcripts were found to be abundant in monocyte-derived dendritic cells and macrophages, treated or not with LPS. Low expression could also be detected by reverse transcription-PCR in CD4+ T lymphocytes. The gene encoding ChemR23 was assigned by radiation hybrid mapping to the q21.2-21.3 region of human chromosome 12, outside the gene clusters identified so far for chemoattractant receptors. Given the increasing number of chemoattractant receptors used by HIV-1, HIV-2 and SIV as coreceptors, ChemR23 was tested in fusion assays for potential coreceptor activity by a range of viral strains. None of the tested HIV-2 strains made use of ChemR23 as a coreceptor, but several SIV strains (SIVmac316, SIVmac239, SIVmacl7E-Fr and SIVsm62A), as well as a primary HIV-1 strain (92UG024-2) used it efficiently. ChemR23 therefore appears as a coreceptor for immunodeficiency viruses that does not belong to the chemokine receptor family. It is also a putative chemoattractant receptor relatively specific for antigen-presenting cells, and it could play an important role in the recruitment or trafficking of these cell populations. Future work will be required to identify the ligand(s) of this new G protein-coupled receptor and to define its precise role in the physiology of dendritic cells and macrophages.
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PMID:ChemR23, a putative chemoattractant receptor, is expressed in monocyte-derived dendritic cells and macrophages and is a coreceptor for SIV and some primary HIV-1 strains. 960 76

The changes in type 1 (IL12, IFN gamma, IL2) and type 2(IL4, IL10) cytokine profiles may be associated with virological parameters of progression of the disease in HIV-1-infected patients. The production of cytokines was studied in LPS + PHA-activated whole-blood culture in HIV-1-infected individuals at different stages of the disease. The association was investigated between IL12p40 and IL12p70 profiles and other cytokines (IFN gamma, IL4, IL10), as well as the isolation of cytopathogenic HIV-1 strains. The phenotype of HIV strains was studied by a micromethod based on P4 cell line, allowing detection of cytopathic effects of HIV-1 isolates (syncytium-induction and cell-killing without syncytium induction). The individual variations in IL12p40 and IL12p70 production were limited in the healthy controls. Low values were observed in HIV-1-infected patients. The production of IL12 (p40 and p70) and the IL12p70/IL4 ratio and the IFN gamma/IL4 ratio were significantly lower in patients with cytopathic isolates compared with patients with noncytopathic isolates, and a correlation was obtained between the values of IL12 (IL12p40 and IL12p70) and those of IFN gamma/IL4 ratio. There was no increase in the secretion of IL4 and IL10 in patients with cytopathic strains compared with other patients. The results indicate a decreased production of type 1 cytokines (IL12, IFN gamma) in the presence of a relatively preserved production of type 2 cytokines (IL4, IL10) in HIV-1-infected patients. In conclusion, the defect of production of IL12 by whole blood is associated with virological correlates of progression of HIV-1 disease.
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PMID:A decreased production of IL12 in vitro is associated with isolation of cytopathic HIV-1 strains in HIV-1-infected patients. 962 8

We recently reported that LPS stimulation of monocytic cells leads to the activation of PU.1, a member of the Ets family of transcription factors. Phosphorylation of PU.1 by protein kinase CK2 was found to up-regulate its trans-activation function, but not its DNA binding activity. Previous studies suggested that Ets proteins could bind to NF-kappa B motifs at the tetrameric core sequence TTCC. In macrophages, LPS-inducible HIV-1 gene expression is mediated in part by binding of NF-kappa B to identical tandem binding sites located within the long terminal repeat (LTR). Thus, we performed additional studies to determine whether PU.1 also played a role in regulating HIV-1 gene expression in macrophages. Our functional studies revealed that activation of the HIV-1 LTR in LPS-stimulated cells requires both NF-kappa B and PU.1. Extensive mutagenesis of the HIV-1 LTR revealed that PU.1-dependent activation requires the Ets motif within the upstream NF-kappa B site, whereas NF-kappa B itself binds to the downstream site. We also found that insertion of five additional nucleotides between the NF-kappa B sites abolished LPS inducibility, suggesting a direct interaction between factors that bind these sites. Lastly, we found that mutation of PU.1 at serine 148, which prevents its phosphorylation by CK2, blocked its ability to activate the HIV-1 LTR in response to LPS. These effects were promoter specific because PU.1 did not affect LPS-inducible activation of a distinct NF-kappa B-dependent promoter. While these data do not demonstrate direct binding of PU.1 to the HIV-1 LTR, they illustrate a novel role for PU.1 in activation of the HIV-1 LTR by LPS.
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PMID:Both PU.1 and nuclear factor-kappa B mediate lipopolysaccharide- induced HIV-1 long terminal repeat transcription in macrophages. 964 33

The HIV-1 promoter was used as a model to identify transcription factors involved in LPS-dependent transcription in RAW 264 murine macrophages. Expression plasmids for Ets-2 and PU.1 trans-activated the HIV-1 LTR and recombinant PU.1 and an Ets-2 DNA binding domain/GST fusion protein bound to the 5' kappa B site of the HIV-1 enhancer. Ets-2 mRNA was LPS-inducible in RAW 264 cells and LPS stimulated phosphorylation of threonine 72 residue within the Ets-2 pointed domain. Induction of Ets-2 and other LPS-responsive transcription factors was also observed upon addition of plasmid DNA, which complicates interpretation of transient transfections. The proximal promoter region, containing two Sp1 sites, was also LPS-responsive. We propose that the kappa B elements and the tandem Sp1 sites act as LPS response elements and that kappa B-mediated LPS action involves Ets and rel factors.
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PMID:Involvement of Ets, rel and Sp1-like proteins in lipopolysaccharide-mediated activation of the HIV-1 LTR in macrophages. 965 43

Melanocortins are proopiomelanocortin-derived peptides that include adrenocorticotropic hormone [ACTH (1-39)], alpha-melanocyte-stimulating hormone [alpha-MSH (1-13)], and related amino acid sequences. Melanocortin peptides have potent antiinflammatory/anticytokine activity. Because cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF) can be detrimental in HIV-infected patients, we investigated the effects of melanocortins on production of IL-1 and TNF alpha in the blood of HIV patients. Cytokine production was measured in whole blood samples stimulated with LPS in the presence or absence of alpha-MSH (1-13), alpha-MSH (11-13), ACTH (1-24), or ACTH (1-39). Melanocortins reduced production of both cytokines in a concentration-dependent fashion. In separate experiments on normal peripheral blood mononuclear cells (PBMC), alpha-MSH (1-13) inhibited production of IL-1 beta and TNF alpha induced by HIV envelope glycoprotein gp 120. These results suggest that stimulation of melanocortin receptors in inflammatory cells could be a novel way to reduce production of cytokines that promote HIV replication.
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PMID:Melanocortin peptides inhibit production of proinflammatory cytokines in blood of HIV-infected patients. 970 Jul 61

Filgrastim induces lymphocytosis, including all T cell subsets, and increased ex vivo interleukin (IL)-2 release as well as lymphocyte proliferation. Since Filgrastim is increasingly used in patients with human immunodeficiency virus (HIV) infection, the effect of Filgrastim on ex vivo cytokine production was determined. Whole blood from 8 healthy volunteers, 5 high-risk volunteers, and 31 HIV-infected outpatients was assayed for cytokine production in response to endotoxin (LPS) or staphylococcal enterotoxin B (SEB) in the presence or absence of 100 ng/mL Filgrastim. LPS-inducible blood cytokine release of HIV-infected patients was not different from that of normal or high-risk volunteers. The suppressive effect of Filgrastim on LPS-inducible blood tumor necrosis factor-alpha and interferon-gamma formation in normal volunteers was not found in HIV-infected patients. Patients with advanced HIV infection showed reduced IL-2 and IL-4 release in the presence of SEB. In the presence of Filgrastim, IL-2 production was partially restored.
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PMID:Filgrastim restores interleukin-2 production in blood from patients with advanced human immunodeficiency virus infection. 972 36

Cells of the monocyte/macrophage lineage are the first targets of HIV-1 in patients and also serve as reservoirs for the virus during the course of infection. We investigated the effects of cell activation on early events of HIV-1 infection of monocyte-derived macrophages. Addition of LPS, a potent stimulator of macrophages, at the time of infection stimulated entry of HIV-1 into monocyte-derived macrophages, as judged by accumulation of early products of RT, but inhibited the synthesis of late RT products and strongly repressed nuclear import of the viral DNA, resulting in protection from infection. This effect was mediated by the CD14 receptor and involved activation of the p38 mitogen-activated protein kinase pathway. Disruption of this signaling pathway using a specific inhibitor of the p38 mitogen-activated protein kinase (SB203580) restored HIV-1 infection in the presence of LPS. These results suggest a novel view of the role of macrophage activation in anti-HIV responses of the immune system.
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PMID:Activation-induced resistance of human macrophages to HIV-1 infection in vitro. 988 13

The cognitive and motor impairments of HIV-1-associated dementia (HAD) often result from neuronal damage of drop-out. In the infected human host, virus-infected immune-competent mononuclear phagocytes (MPs) (brain macrophages and microglia) are the target cells for HIV-1 and the producers of bioactive molecules that mediate neural damage. Indeed, in laboratory experiments, activated HIV-1-infected macrophages placed into human or rodent brain tissues induce neuronal apoptosis. Nonetheless, the mechanisms for neuronal dysfunction in HAD have yet to be discerned. To these ends, we studied the effects of HIV-1-infected monocyte-derived macrophage (MDM) secretions, electrophysiologically, on neuronal synaptic transmission. Bath application of HIV-1-infected MDM culture fluids onto rat hippocampal brain slices resulted in inhibition of evoked field excitatory postsynaptic potentials (EPSPs). In contrast, fluids from uninfected MDMs showed mild effects on the EPSPs. HIV-1-associated inhibition of EPSPs was enhanced by LPS activation, both for HIV-1-infected and uninfected MDMs. Importantly, paired-pulse facilitation ratio tests showed that factors secreted by HIV-1-infected MDMs acted transiently on presynaptic terminals, providing insights into the site of action and mechanism of the MDM-induced neuronal dysfunction. These results, taken together, demonstrate that factors produced as a consequence of MDM infection and activation affect neuronal synaptic transmission.
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PMID:Unraveling the mechanisms of neurotoxicity in HIV type 1-associated dementia: inhibition of neuronal synaptic transmission by macrophage secretory products. 1002 53

CC chemokine receptor 5 (CCR5) is a cell entry cofactor for macrophage-tropic isolates of human immunodeficiency virus 1 (HIV-1). An inactive CCR5 allele with a 32-nucleotide deletion (CCR5Delta32) has been described that confers resistance to HIV-1 infection in homozygotes and slows the rate of progression to AIDS in heterozygotes. We found the allele CCR5Delta32 to be not rare in 399 Swiss blood donors with a frequency of 0.080. To assess the influence of defective CCR5 on production of its ligands we determined the capacity to produce the chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES in comparison with the production of the CXC chemokine IL-8 which does not bind to CCR5. Production of chemokines was determined during endotoxin stimulation of whole-blood samples ex vivo. Both, basal and LPS-induced chemokine production in 32 blood donors heterozygous for CCR5Delta32 were not significantly different when compared with 55 blood donors who were homozygous for the wild type CCR5 allele.
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PMID:Heterozygous defect in HIV-1 coreceptor CCR5 and chemokine production. 1008 Aug 73

Several groups, including ours, have reported that chloroquine (CQ) or its analog hydroxychloroquine has anti-HIV-1 activity both in vitro and in vivo. We studied in vitro whether the addition of CQ to the combination of hydroxyurea (HU) plus didanosine (ddI) had an additive effect in inhibiting the replication of HIV-1. Therefore both the H-9 T lymphocytic cell line and the U-937 promonocytic cell line as well as primary T cells and monocytes were infected with HIV-1 and then treated with HU at 0.2 mM and ddI at 1 microM and varying concentrations of CQ. Addition of CQ resulted in an additional inhibition of HIV-1 replication, as assessed by reverse transcriptase (RT) activity, with a CQ EC50 of 0.4-0.9 microM for the cell lines and of 0.2-0.9 microM for the primary cells. Similarly, addition of CQ further inhibited HIV-1 replication in U-1 cells stimulated either with LPS or H2O2 and in ACH-2 cells stimulated either with PMA or H2O2, with CQ EC50 values of 0.1 and 1 microM, respectively. Under the experimental conditions used, CQ induced neither toxicity nor apoptosis in the H-9 and U-937 cells. This in vitro additive anti-HIV-1 activity of CQ, in combination with HU + ddI, supports the idea that this triple regimen should be studied in clinical trials. It may become of particular interest to HIV-1-infected individuals from the developing world, in view of the low cost of both CQ and HU.
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PMID:Chloroquine exerts an additive in vitro anti-HIV type 1 effect when associated with didanosine and hydroxyurea. 1050 72


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