Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among genes that influence human susceptibility to HIV (human immunodeficiency virus) infection or AIDS (acquired immunodeficiency syndrome) progression, chemokine-receptor and chemokine genes were extensively studied because of their role as HIV co-receptors or co-receptor competitors, respectively. We have studied in non-human primates (chimpanzee, gorilla, gibbon, orang-utan, crab-eating and rhesus macaque, baboon and marmoset) the RANTES, CCR2 and CX3CR1 gene sequences in regions surrounding human mutations that were associated with susceptibility to HIV or AIDS progression: RANTES G-403A and C-28G, CCR2 V64I, CX3CR1 V249I and CX3CR1 T280M. Among these five dimorphisms, only RANTES G-403A is observed in one of the eight primate species studied here (gibbon). This suggests that these mutations appeared recently in humans and probably do not account for variable HIV/SIV disease progression in primates. It is noteworthy that chimpanzees, which are naturally resistant to HIV-1- and HIV-2-induced AIDS, do not have the human mutations associated with delayed disease progression. Inter-species and intra-species polymorphic positions are observed in primates and we discuss the potential impact of these mutations on HIV/SIV disease progression. Particularly, we identified polymorphisms in old-world monkey (OWM) genes, and it could be of great importance to analyse the possible association between these polymorphisms and disease progression in OWM species that are currently used in research for HIV vaccine and therapy.
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PMID:Polymorphism of human and primate RANTES, CX3CR1, CCR2 and CXCR4 genes with regard to HIV/SIV infection. 1287 9

Entry of human immunodeficiency type 1 virus (HIV-1) into target cells requires both CD(4)and one of the chemokine receptors. Viruses predominantly use one, or occasionally both, of the major co-receptors CCR5 and CXCR4, although other receptors, including CCR2B and CCR3, function as minor co-receptors. A 32-nucleotide deletion (D32) within the b-chemokine receptor 5 gene (CCR5) has been described in subjects who remain uninfected despite extensive exposition to HIV-1. The heterozygous genotype delays disease progression. This allele is common among Caucasians, but has not been found in people of African or Asian ancestry. A more common transition involving a valine to isoleucine switch in transmembrane domain I of CCR2B (64I), with unknown functional consequences, was found to delay disease progression but not to reduce infection risk. As the Brazilian population consists of a mixture of several ethnic groups, we decided to examine the genotype frequency of these polymorphisms in this country. There were 11.5% CCR5 heterozygotes among the HIV-1 infected population and 12.5% among uninfected individuals, similar to data from North America and Western Europe. The prevalence of CCR2-64I homozygotes and heterozygotes was 0.06 and 15.2%, respectively, also similar to what is known for North America and Western Europe.
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PMID:Frequency of polymorphisms of genes coding for HIV-1 co-receptors CCR5 and CCR2 in a Brazilian population. 1453 83

The role that host genetics plays in the modification of the rate of human immunodeficiency virus 1 (HIV-1)-related disease progression was evaluated in a seroprevalent cohort of 1049 children with symptomatic HIV-1 infection who participated in 2 clinical trials in the United States. Variants including CCR2-V64I, CCR5-wt/Delta32, CCR5-59029-G/A, CCR5-59353-T/C, CCR5-59356-C/T, and SDF1-3'-G/A were identified by polymerase chain-reaction genotyping. Children with the CCR5-wt/Delta32 genotype experienced significantly delayed disease progression, including less neurocognitive impairment. In the CCR5-wt/wt group, the most rapid disease progression was in those with the CCR5-59029-A/A genotype, which was present in 23% of the children. Although the SDF1-3'-A/A variant was associated with more-rapid disease progression, it occurred in <2% of the children studied. Modest or little impact was associated with the CCR5-59353, CCR5-59356, or CCR2 genotypes. Thus, in children with the CCR5-wt/wt genotype, variants at CCR5-59029 have the broadest impact on disease progression. These data suggest that, in children, host genetics plays an important role in HIV-1-related disease progression and neurological impairment.
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PMID:Genetic influence of CCR5, CCR2, and SDF1 variants on human immunodeficiency virus 1 (HIV-1)-related disease progression and neurological impairment, in children with symptomatic HIV-1 infection. 1462 71

Stable gene silencing by RNA interference (RNAi) can be achieved by expression of small hairpin RNAs (shRNAs) from RNA polymerase III promoters. We have tested lentiviral vectors expressing shRNAs targetting CCR5 in primary CD4 T cells from donors representing various CCR5 and CCR2 genetic backgrounds covering the full spectrum of CCR5 expression levels and permissiveness for HIV-1 infection. A linear decrease in CCR5 expression resulted in a logarithmic decrease in cellular infection, giving up to three logs protection from HIV-1 infection in vitro. Protection was maintained at very high multiplicity of infection. This and other recent reports on RNAi should open a debate about the use of RNAi gene therapy for HIV infection.
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PMID:Protection from HIV-1 infection of primary CD4 T cells by CCR5 silencing is effective for the full spectrum of CCR5 expression. 1464 Mar 83

The identification of chemokine receptors as HIV-1 coreceptors has focused research on developing strategies to prevent HIV-1 infection. We generated CCR2-01, a CCR2 receptor-specific monoclonal antibody that neither competes with the chemokine CCL2 for binding nor triggers signaling, but nonetheless blocks replication of monotropic (R5) and T-tropic (X4) HIV-1 strains. This effect is explained by the ability of CCR2-01 to induce oligomerization of CCR2 with the CCR5 or CXCR4 viral coreceptors. HIV-1 infection through CCR5 and CXCR4 receptors can thus be prevented in the absence of steric hindrance or receptor downregulation by acting in trans on a receptor that is rarely used by the virus to infect cells.
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PMID:Blocking HIV-1 infection via CCR5 and CXCR4 receptors by acting in trans on the CCR2 chemokine receptor. 1468 76

Several chemokines and chemokine receptors are involved in HIV-1 infection, disease progression, and transmission. We studied the prevalence of genetic variations in CCR2, SDF1, and the CCR5 gene and its promoter region at positions 59029, 59353, and 59356 in a seroprevalent cohort of 1057 children with symptomatic HIV-1 infection in the United States. The percentage of children with the CCR5-wt/Delta32 genotype was significantly higher for white, non-Hispanic children (15%) than for Hispanic (6%) or black, non-Hispanic children (4%). For the CCR5-59029-G/A, CCR5-59353-T/C, and CCR5-59356-C/T polymorphisms, there were significant or marginally significant differences in genotype frequencies across race/ethnicity groups. For the CCR2-wt/64I polymorphism, both black, non-Hispanic and Hispanic children had a higher frequency of the CCR2-wt/64I genotype (24% and 21%, respectively) and CCR2-64I/64I genotype (4% and 3%, respectively) than white, non-Hispanic children (14% and 2%, respectively). For the SDF1-3'-G/A polymorphism, black, non-Hispanic children had a lower combined frequency of the SDF1-3'-G/A and SDF1-3'-A/A genotypes (15%) than did Hispanic children (33%) and white, non-Hispanic children (37%). These analyses show that the distribution of chemokine receptor and chemokine genetic polymorphisms varies significantly across race/ethnicity subgroups of HIV-1-infected children in the United States.
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PMID:Prevalence of chemokine and chemokine receptor polymorphisms in seroprevalent children with symptomatic HIV-1 infection in the United States. 1507 47

Genetic polymorphisms of CCR5, CCR2, and SDF1 genes have been associated with resistance during human immunodeficiency virus type 1 (HIV-1) infection and disease progression. In the present report, we studied the frequency and co-occurrence of CCR5Delta32, CCR5-59029A/G, CCR2-64I, and SDF1-3'A allelic variants among HIV-1-seronegative individuals (n = 171) in Moscow. Observed allelic frequencies were 0.0906 [95% confidence interval (CI), 0.06-0.1212] for CCR5Delta32, 0.4072 (95% CI, 0.3542-0.4602) for CCR5-59029G, 0.1061 (95% CI, 0.0728-0.1394) for CCR2-64I, and 0.2218 (95% CI 0.1715-0.2721) for SDF1-3'A. A significant linkage disequilibrium (p = 0.0034) between CCR2-64I and SDF1-3'A alleles was observed.
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PMID:Prevalence of alleles associated with HIV resistance in Russia. 1514 Mar 77

To investigate African long-term survivors (LTSs) infected with non-subtype B human immunodeficiency virus type 1 (HIV-1), we obtained full-length HIV-1 RNA sequences and immunogenetic profiles from 6 untreated women enrolled in the Pumwani Sex Worker Cohort in Nairobi, Kenya. There were no discernible sequence changes likely to cause attenuation. CCR2-V64I, an immunogenetic polymorphism linked to LTSs, was detected in 4 women, all of whom carried the HLA B58 allele. Further investigation of 99 HIV-1-infected Nairobi women found an association between CCR2-V64I and HLA B58 (P=.0048). Studying the interaction among immunogenetics, immune responses, and viral sequences from all HIV-1 subtypes may increase our understanding of slow HIV-1 disease progression.
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PMID:Long-term survivors in Nairobi: complete HIV-1 RNA sequences and immunogenetic associations. 1527 96

Both antiretroviral therapy and the human coreceptor polymorphism CCR2-V64I slow progression of human immunodeficiency virus type 1 (HIV-1) disease. To examine the effect of V64I on disease progression in patients receiving therapy, we determined CCR2 genotypes in the Women's Interagency HIV Study cohort. We studied 2047 HIV-1-infected women, most of whom initiated treatment during the study. No association was seen between CCR2 genotype and either disease progression or therapeutic response, suggesting that the benefits of treatment most likely overshadow the salutary effects of the V64I polymorphism.
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PMID:CCR2 genotype and disease progression in a treated population of HIV type 1-infected women. 1547 20

Here we report that the N-pyridinylmethyl cyclam analog AMD3451 has antiviral activity against a wide variety of R5, R5/X4, and X4 strains of human immunodeficiency virus type 1 (HIV-1) and HIV-2 (50% inhibitory concentration [IC(50)] ranging from 1.2 to 26.5 microM) in various T-cell lines, CCR5- or CXCR4-transfected cells, peripheral blood mononuclear cells (PBMCs), and monocytes/macrophages. AMD3451 also inhibited R5, R5/X4, and X4 HIV-1 primary clinical isolates in PBMCs (IC(50), 1.8 to 7.3 microM). A PCR-based viral entry assay revealed that AMD3451 blocks R5 and X4 HIV-1 infection at the virus entry stage. AMD3451 dose-dependently inhibited the intracellular Ca(2+) signaling induced by the CXCR4 ligand CXCL12 in T-lymphocytic cells and in CXCR4-transfected cells, as well as the Ca(2+) flux induced by the CCR5 ligands CCL5, CCL3, and CCL4 in CCR5-transfected cells. The compound did not interfere with chemokine-induced Ca(2+) signaling through CCR1, CCR2, CCR3, CCR4, CCR6, CCR9, or CXCR3 and did not induce intracellular Ca(2+) signaling by itself at concentrations up to 400 microM. In freshly isolated monocytes, AMD3451 inhibited the Ca(2+) flux induced by CXCL12 and CCL4 but not that induced by CCL2, CCL3, CCL5, and CCL7. The CXCL12- and CCL3-induced chemotaxis was also dose-dependently inhibited by AMD3451. Furthermore, AMD3451 inhibited CXCL12- and CCL3L1-induced endocytosis in CXCR4- and CCR5-transfected cells. AMD3451, in contrast to the specific CXCR4 antagonist AMD3100, did not inhibit but enhanced the binding of several anti-CXCR4 monoclonal antibodies (such as clone 12G5) at the cell surface, pointing to a different interaction with CXCR4. AMD3451 is the first low-molecular-weight anti-HIV agent with selective HIV coreceptor, CCR5 and CXCR4, interaction.
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PMID:Inhibition of human immunodeficiency virus replication by a dual CCR5/CXCR4 antagonist. 1554 51


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