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

We compared the density of the CCR5 receptor on the surface of CD4+ lymphocytes and monocytes/macrophages of the homozygote (CCR5-59653C) and the heterozygote (CCR5-59653T), bearing CCR2-64V alleles. Flow cytometric analysis revealed lower density of the CCR5 receptor on the surface of CD4+ lymphocytes and monocytes/macrophages of the heterozygote than in the same cells of the homozygote. Our observation might explain slower replication of HIV and the delay in progression to AIDS in the individuals bearing CCR5-59653T transition.
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PMID:Decreased density of the CCR5 receptor on the surface of CD4+ lymphocytes and monocytes/macrophages is associated with the CCR5-59653T transition in the promoter region. 1205 98

The genetic control of HIV infection by the host involves a certain number of genes, among which those which code for chemokines/chemokines receptors, cytokines, MHC. Genes such as CCR5, CCR2, SDF1, and more recently CX3CR1 received great attention from several laboratories including ours, since they play a role as HIV coreceptor and, as such, on the infectivity of the host. In addition, it was shown that the polymorphism of these genes influences the evolution of infection, whether they have a protective or deleterious effect. Results obtained by our laboratory on the genetic polymorphism and its implication in HIV infection will be reported herein. Furthermore, to better understand their role, we looked for the capacities that the chemokines may have to play an immunomodulatory function, independently of their chemoattractive effect. In two examples, we showed that chemokines influence notably the cellular immune functions, such as CD8 cytotoxicity (Rantes/CCR3) and gamma interferon production (fractalkine/CX3CR1). Globally, the results indicate that chemokines/chemokines receptors polymorphism represent important epidemiological factors, but also contributes to evaluate the prognosis of HIV infection, through a better understanding of the disease physiopathology.
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PMID:[Chemokines and immunomodulation: applications for HIV infections]. 1213 37

A single nucleotide polymorphism (SNP) at codon 64 in the CC chemokine receptor 2 gene (CCR2 V64I) has been associated with a dominant effect of delaying disease progression from human immunodeficiency virus-1 (HIV-1) infection to acquired immunodeficiency syndrome (AIDS). The objective of our study was to design a comprehensive mutation detection assay for the entire coding region of the CCR2A and CCR2B gene transcripts, including all relevant splice site junctions and to identify novel mutations and SNPs within our predominantly African-based population, which could influence an individual's susceptibility to HIV-1 infection and/or progression to AIDS. The mutation detection assay, based on denaturing gradient gel electrophoresis (DGGE), allowed for the complete analysis of five individuals per denaturing gel. Our study cohort consisted of 102 HIV seropositive patients and 144 HIV seronegative controls from the diverse South African population. Application of the CCR2-DGGE assay resulted in the detection of two previously reported CCR2 polymorphisms, namely CCR2 V64I and CCR2 N260N, and 11 novel mutations, including seven SNPs occurring at high allelic frequencies within specific population groups of South Africa. The large number of novel mutations/SNPs identified, using the CCR2-DGGE assay, indicates the importance for comprehensive analysis of all candidate genes in host susceptibility to HIV-1 infection, specifically in the under-studied African-based populations.
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PMID:Novel mutations and SNPs identified in CCR2 using a new comprehensive denaturing gradient gel electrophoresis assay. 1232 20

Macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta are highly related members of the CC chemokine subfamily. Despite their structural similarities, MIP-1alpha and MIP-1beta show diverging signaling capacities. Depending on the MIP-1 subtype and its NH(2)-terminal processing, one or more of the CC chemokine receptors CCR1, CCR2, CCR3 and CCR5 are recognized. Since both human MIP-1alpha subtypes (LD78alpha and LD78beta) and MIP-1beta signal through CCR5, the major co-receptor for M-tropic HIV-1 strains, these chemokines are capable of inhibiting HIV-1 infection in susceptible cells. In this review, different aspects of human and mouse MIP-1alpha and MIP-1beta are discussed, including their protein and gene structures, their regulated production, their receptor usage and biological activities and their role in several pathologies including HIV-1 infection.
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PMID:Macrophage inflammatory protein-1. 1240 80

To investigate the influence of the CC chemokine receptor 2 64I and CC chemokine receptor 5 delta32 polymorphisms on the virologic and immunologic response of human immunodeficiency virus type 1 (HIV-1)-infected patients to highly active antiretroviral therapy, data from 4 clinical studies were pooled. The prevalence of the CCR5 delta32 polymorphism was 21% (27 of 130 subjects), and the prevalence of the CCR2 64I polymorphism was 15% (19 of 130 subjects). There were no major differences between subjects with and without polymorphisms in the CCR5 and/or CCR2 genes with respect to the rate of initial viral clearance, proportion of subjects with plasma HIV-1 RNA levels below the lower limit of quantification, rate of virologic treatment failure, immunologic responses, and disease progression during 96 weeks of follow-up.
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PMID:CC chemokine receptor 5 delta32 and CC chemokine receptor 2 64I polymorphisms do not influence the virologic and immunologic response to antiretroviral combination therapy in human immunodeficiency virus type 1-infected patients. 1244 57

The G-protein coupled receptor CCR5 is the main co-receptor for macrophage-tropic HIV-1 strains. I have built a structural model of the chemokine receptor CCR5 and used it to explain the binding and selectivity of the antagonist TAK779. Models of the extracellular (EC) domains of CCR5 have been constructed and used to rationalize current biological data on the binding of HIV-1 and chemokines. Residues spanning the transmembrane region of CCR5 have been modeled after rhodopsin, and their functional significance examined using the evolutionary trace method. The receptor cavity shares six residues with CC-chemokine receptors CCR1 through CCR4, while seven residues are unique to CCR5. The contribution of these residues to ligand binding and selectivity is tested by molecular docking simulations of TAK779 to CCR1, CCR2, and CCR5. TAK779 binds to CCR5 in the cavity formed by helices 1, 2, 3, and 7 with additional interactions with helices 5 and 6. TAK779 did not dock to either CCR1 or CCR2. The results are consistent with current site-directed mutagenesis data and with the observed selectivity of TAK779 for CCR5 over CCR1 and CCR2. The specific residues responsible for the observed selectivity are identified. The four EC regions of CCR5 have been modeled using constrained simulated annealing simulations. Applied dihedral angle constraints are representative of the secondary structure propensities of these regions. Tertiary interactions, in the form of distance constraints, are generated from available epitope mapping data. Analysis of the 250 simulated structures provides new insights to the design of experiments aimed at determining residue-residue contacts across the EC domains and for mapping CC-chemokines on the surface of the EC domains.
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PMID:Structure modeling of the chemokine receptor CCR5: implications for ligand binding and selectivity. 1249 74

Several studies have investigated whether heterozygosity for a 32-basepair deletion in the CC chemokine receptor 5 gene (CCR5-Delta32 ) affects susceptibility to perinatal HIV-1 infection, but results have been inconclusive. We performed a meta-analysis of published data from 11 studies of HIV-1 perinatally exposed children who were genotyped for the CCR5-Delta32 polymorphism. The crude overall HIV-1 infection rates, by simple data pooling, were 20% (one of five) amongCCR5-Delta32 homozygote children, 39% (131 of 335) among CCR5-Delta32 heterozygote children, and 40% (1408 of 3526) among wild-type CCR5 homozygote children. Compared with wild-type homozygotes, the random effects risk ratio for heterozygotes was 1.04 (95% confidence interval [CI], 0.92-1.17) among all children (N = 3861) and 1.03 (95% CI, 0.90-1.17) among those of European descent (n = 2890). Results were similar when adjusted for the available data on the CCR2-641 polymorphism (n = 1542). The meta-analysis clarifies that perinatal infection is not significantly altered by heterozygosity for CCR5-Delta32 in the child.
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PMID:Effect of CCR5-delta32 heterozygosity on the risk of perinatal HIV-1 infection: a meta-analysis. 1251 16

Chemokines are key mediators of the selective migration of leukocytes that occurs in neurodegenerative diseases and related inflammatory processes. Astrocytes, the most abundant cell type in the CNS, have an active role in brain inflammation. To ascertain the role of astrocytes during neuropathological processes, we have investigated in two models of primary cells (human fetal and simian adult astrocytes) the repertoire of chemokines and their receptors expressed in response to inflammatory stimuli. We demonstrated that, in the absence of any stimulation, human fetal and simian adult astrocytes express mRNA for receptors APJ, BOB/GPR15, Bonzo/CXCR6, CCR2, CCR3, CCR5, CCR8, ChemR23, CXCR3/GPR9, CXCR4, GPR1, and V28/CX3CR1. Moreover, TNFalpha and IL-1beta significantly increase BOB/GPR15, CCR2, and V28/CX3CR1 mRNA levels in both models. Furthermore, TNFalpha and IFNgamma act synergistically to induce expression of the major coreceptors for HIV infection, CXCR4 and CCR5, at both the mRNA and protein levels in human and simian astrocytes, whereas CCR3 expression was not affected by cytokine treatment. Finally, TNFalpha/IFNgamma was the most significant cytokine combination in leading to a pronounced upregulation in a comparable, time-dependent manner of the production of chemokines IP-10/CXCL10, RANTES/CCL5, MIG/CXCL9, MCP-1/CCL2, and IL-8/CXCL8. In summary, these data suggest that astrocytes serve as an important source of chemokines under the dependence of a complex cytokine regulation, and TNFalpha and IFNgamma are important modulators of chemokines and chemokine receptor expression in human as well as simian astrocytes. Finally, with the conditions we used, there was no difference between species or age of tissue.
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PMID:Expression of chemokines and their receptors in human and simian astrocytes: evidence for a central role of TNF alpha and IFN gamma in CXCR4 and CCR5 modulation. 1255 3

A model was constructed that estimates the probability of an HIV-infected individual developing AIDS or dying within a certain time span if left untreated, based on the most recent CD4 lymphocyte count, HIV-1 RNA load, and HIV-1 phenotype, together with age, time since seroconversion, and two genetic cofactors. The model helps clinicians in deciding when to start highly active antiretroviral treatment (HAART). Data from the Amsterdam Cohort Study among homosexual men restricted to individuals with an estimated date of seroconversion (N = 280) were used. Individual predictions based on several combinations of marker and cofactor values were obtained, and their accuracy was measured using two indices of predictive value. CD4 lymphocyte count and HIV RNA load have the highest predictive value and act independently. The predictive value of the HIV phenotype is only slightly lower and greatly enhances predictions at high CD4 counts. The CCR5-Delta32 and CCR2-64I alleles have no additional predictive value. Some predictive value is lost by not knowing time since seroconversion, and some effect of calendar period is present. In summary, for prognosis, the markers CD4 count, HIV-1 RNA load, and HIV-1 phenotype (at a high CD4 count) are equally important, and the genetic cofactors considered are of no use.
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PMID:Prediction of residual time to AIDS and death based on markers and cofactors. 1267 3

Essential hypertension is a complex trait under polygenic control. Evidences suggests immune system involvement during pathogenesis. CC-chemokine receptor (CCR)5 and CCR2 are characterised by gene polymorphism. Variant alleles are derived from a deletion in the CCR5 gene (CCR5delta32) and a substitution mutation at the CCR2 locus (CCR264I). CCR polymorphic forms have been studied extensively as invasion cofactors for HIV-1, but they have also been implicated in immuno-related disorders. Here, we evaluate the allelic distribution of CCR5 and CCR2 genes in essential hypertension in a case-control study. Genotype frequency in a group of essential hypertensive patients (stage I-II; n=120) and a group of unrelated, healthy Caucasian subjects (n=340) is compared. CCR gene polymorphism is analysed by polymerase chain reaction and restriction enzyme digestion. A statistically significant difference was observed for CCR5 and CCR2 mutant alleles in essential hypertensive patients, compared with the controls (P=0.004 and P=0.003, respectively). CCR5delta32 and CCR264I alleles showed a 0.096 and 0.10 frequency among cases. To date, a role for the immune system in hypertension has not been clarified, nor has the predictive value of CCR polymorphisms.
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PMID:CCR5 and CCR2 gene polymorphisms in hypertensive patients. 1268 Jun 26


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