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

Susceptibility to HIV-1 infections is, beside other factors, determined by individual host genetic variants like HLA class I alleles, CCR5 and CCR2 variants and levels of CCR5 binding chemokines. A new approach to determine the individual risk of acquiring an HIV infection or to estimate the disease progression could now be possible. In a recent study, a significant interindividual and interpopulation difference in the copy number of a segmental duplication encompassing the gene encoding CCL3L1, a potent human immunodeficiency virus-1 (HIV- 1)-suppressive chemokine was found. Possession of a CCL3L1 copy number lower than the population average was associated with markedly enhanced HIV/acquired immunodeficiency syndrome (AIDS) susceptibility. This could lead to a screening test that identifies people who have a higher or lower susceptibility to HIV/ AIDS, potentially enabling clinicians to adapt treatment regimens. Also, this is particularly important for assessment of the efficacy of a protective vaccine.
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PMID:Susceptibility to HIV/AIDS: an individual characteristic we can measure? 1594 Apr 20

Chemokine receptor genetic mutations are among the factors which have been shown to influence human susceptibility to HIV-1 infection and progression. The CCR2-64I mutation has been shown to delay HIV-1 disease progression in some studies. Here we show evidence of delayed disease progression, reflected in maintenance of a stable viral load and a slow CD4 T-cell decline, in a patient with the CCR2-64I gene. We then consider the potential value of identifying these genetic defects in the era of fusion/entry inhibiting therapeutics.
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PMID:CCR2/64I mutation detection in a HIV-1-positive patient with slow CD4 T-cell decline and delay in disease progression. 1594 75

Limited information is available on the prevalence among rural Africans of host genetic polymorphisms conferring resistance to HIV-1 infection or slowing HIV disease progression. We report the allelic frequencies of the AIDS-related polymorphisms CCR2-64I, SDF1-3'A, and CCR5-Delta32 in 321 volunteers from 7 ethnic groups in Cameroon. Allelic frequencies differed among the 7 ethnic groups, ranging from 10.8% to 31.3% for CCR2-64I and 0.0% to 7.1% for SDF1-3'A. No CCR5-Delta32 alleles were found. HIV seroprevalence was 6.9% in the total population and peaked at younger ages in girls and women than in boys and men. Among 15- to 54-year-olds, HIV seroprevalence varied from 2.0% to 11.1% among the village populations. Conditional logistic regression analysis using data from boys and men aged 15 to 54 years showed the number of CCR2-64I alleles to be a significant risk factor for HIV seropositivity (odds ratio per allele adjusted for age and matched on ethnic group = 6.3, 95% confidence interval: 1.3-30.3); this association was not found in women. The findings are consistent with the hypothesis that CCR2-64I alleles may delay HIV disease progression without affecting susceptibility to infection among men. We did not observe this relation among women, and other factors, such as multiple pregnancies or maternal stressors (eg, breastfeeding), may have masked any protective effect of CCR2-64I alleles. Further study of this issue among women is warranted. SDF1-3'A did not differ between HIV-seropositive and HIV-seronegative individuals but was associated with increasing age among HIV-seronegative women, suggesting a protective effect against HIV-1 infection.
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PMID:Distribution of CCR2-64I and SDF1-3'A alleles and HIV status in 7 ethnic populations of Cameroon. 1612 88

Exposed seronegative individuals (ES) with persistent high-risk sexual behavior may be less susceptible to human immunodeficiency virus type 1 (HIV-1) infection because they carry the chemokine receptor (CR) gene alleles CCR5 open reading frame (ORF) Delta32, CCR5 promoter -2459G, or CCR2 ORF 64I (CCR2-64I), all of which have been found to diminish HIV-1 infectivity and/or disease progression. To investigate this, we determined the haplotypes for these three genetic loci in 93 ES and 247 low-risk control individuals. To test if protective haplotypes exert their effect by modulating CR expression, we measured the protein expression of CCR5 and CXCR4 on circulating CD4+ T cells and CD14+ monocytes in 71 ES and 92 controls. To avoid investigator bias, the analysis was performed without knowledge of each subject's risk and genotype. The CCR5 -2459G allele was significantly enriched in ES Caucasian men, who constituted the majority (84%) of the ES cohort, compared to the control Caucasian men (P = 0.02). This increase was mostly attributable to a higher frequency of the -2459 A/G versus the -2459 A/A genotype in individuals heterozygous for the delta32 allele (P = 0.012). No protective influence of the CCR2-64I allele was observed. The haplotypes CCR5 ORF delta32/CCR5 -2459A (in complete linkage disequilibrium) and CCR5 ORF wt/CCR5 -2459G had a cumulative negative effect on the expression of CCR5, since we measured significantly reduced CCR5 densities on both T-helper cells and monocytes only when both haplotypes were present. Densities of CCR5 on lymphocytes and monocytes were correlated (r = 0.59; P < 0.0001), indicating concordance of CCR5 expression patterns across different cell types. We conclude that the CCR5 ORF delta32/wt-CCR5 -2459 A/G genotype combination offers an advantage in resisting sexual HIV-1 transmission and that this effect is mediated by a relative paucity of CCR5 on potential target cells of HIV-1.
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PMID:Combined effect of CCR5-Delta32 heterozygosity and the CCR5 promoter polymorphism -2459 A/G on CCR5 expression and resistance to human immunodeficiency virus type 1 transmission. 1614 Jul 45

This study used a well characterized cohort of human immunodeficiency virus type 1 (HIV-1)-infected hemophiliacs to define the relationship between the SDF1-3'A allele, the plasma HIV-1 coreceptor tropism, and the natural history of HIV-1 disease. Subjects heterozygous or homozygous for the SDF1-3'A allele experienced higher rates of decline in CD4+ T cell counts over time than did those without the allele (P=.009). Moreover, they had an increased risk of progression to acquired immunodeficiency syndrome and death, a relationship that persisted even when baseline plasma HIV-1 RNA levels and CD4+ T cell counts or CCR5 Delta 32 and CCR2-64I genotype were controlled for. This relationship was even stronger in a subgroup of subjects for whom tropism data were available. Subjects with the SDF1-3'A allele were also more likely to have detectable X4-tropic viruses (P=.012), and, when tropism was included in the survival analyses, the effect of the SDF1-3'A allele on disease progression was no longer significant. Therefore, the increased frequency of X4-tropic viruses in subjects carrying the SDF1-3'A allele may explain the observed adverse effect that this allele has on the natural history of HIV-1 disease.
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PMID:Stromal cell-derived factor-1 genotype, coreceptor tropism, and HIV type 1 disease progression. 1620 74

An interesting finding in the epidemiology of human immunodeficiency virus (HIV) infection is that certain mutations in genes coding for chemokine receptors and their ligands may confer resistance to HIV-1 infection and/or AIDS progression. The mutations most frequently studied are the CCR5-delta32, CCR2-64I and SDF1-3'A. We examined the frequency of the above polymorphisms within the Cretan population, evaluating their contribution to a protective genetic background against HIV infection and progression. Two hundred blood samples were recruited at random among prospective blood donors from Crete. Genotyping was initially performed by polymerase chain reaction (PCR) analysis. CCR2 and SDF-1 PCR-amplified genomic regions were further subjected to restriction fragment length polymorphism (RFLP) analysis for genotype determination. The CCR5-delta32 allele frequency among our study group was 3.25%, although no respective homozygous samples were detected. The screening for the CCR2-64I polymorphism yielded 39 heterozygous (19.5%) and 4 homozygous (2%) subjects, revealing a CCR2-64I allele frequency of 11.75%. Among our 200 PCR-RFLP analysed samples, 73 (36.5%) were found heterozygous and 23 (11.5%) homozygous for the SDF1-3'A mutant variant. The allele frequency of the above polymorphism reached 29.75%. The frequency of the CCR5-delta32 allele among our study population seems to be remarkably lower compared to previously reported frequencies in other Caucasian groups. However, the SDF1-3'A allele frequency shows significantly higher distribution profiles within our study group compared to those observed in other Caucasian-European populations. The indicated difference could be attributed to the increased homogeneity of our population, which is well balanced and dispersed over a small geographical area. Since this polymorphism is related with delayed progression from HIV infection to AIDS, it could be used for prognostic genotyping in HIV infected Cretan individuals.
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PMID:Distribution of HIV/AIDS protective SDF1, CCR5 and CCR2 gene variants within Cretan population. 1628 55

Encephalitis and dementia associated with acquired immunodeficiency syndrome (AIDS) are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, blood-brain barrier (BBB) disruption, and eventual loss of neurons. Little is known about whether human immunodeficiency virus 1 (HIV-1) infection of leukocytes affects their ability to transmigrate in response to chemokines and to alter BBB integrity. We now demonstrate that HIV infection of human leukocytes results in their increased transmigration across our tissue culture model of the human BBB in response to the chemokine CCL2, as well as in disruption of the BBB, as evidenced by enhanced permeability, reduction of tight junction proteins, and expression of matrix metalloproteinases (MMP)-2 and MMP-9. HIV-infected cells added to our model did not transmigrate in the absence of CCL2, nor did this condition alter BBB integrity. The chemokines CXCL10/interferon-gamma-inducible protein of 10 kDa, CCL3/macrophage inflammatory protein-1alpha, or CCL5/RANTES (regulated on activation normal T-cell expressed and secreted) did not enhance HIV-infected leukocyte transmigration or BBB permeability. The increased capacity of HIV-infected leukocytes to transmigrate in response to CCL2 correlated with their increased expression of CCR2, the chemokine receptor for CCL2. These data suggest that CCL2, but not other chemokines, plays a key role in infiltration of HIV-infected leukocytes into the CNS and the subsequent pathology characteristic of NeuroAIDS.
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PMID:CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS. 1643 95

Although polymorphisms of chemokine genes (SDF1, stromal cell-derived factor-1 and RANTES, regulated on activation, normal T cell expressed and secreted) and chemokine-receptor genes (CCR5, CCR2, CX(3)CR1) were shown to be associated with sensitivity to HIV infection and untreated HIV disease progression, their association with the response to highly active antiretroviral therapy (HAART) remains unclear. To explore the possible influence of such polymorphisms on the evolution of AIDS in treated patients, we have studied SDF1-3'A, CCR5Delta32, CCR2-64I, CX(3)CR1-249I, and CX(3)CR1-280M polymorphisms in HIV-infected patients under HAART (n = 169). We studied the evolution of plasma virus load and peripheral T lymphocyte counts in these patients up to 3 years after the initiation of HAART. We observed that some of the genetic polymorphisms studied had an impact on the evolution of these two parameters. After 1 year of HAART, patients with a virological response (undetectable plasma HIV-1 RNA) have a higher frequency of the homozygous SDF1-3'A genotype than other patients (p = 0.005). Similarly, patients with a CD4 increase of over 200/mm(3) from baseline after 1 year of HAART display higher frequencies of homozygous SDF1-3'A (p = 0.035) and homozygous CX(3)CR1-280M genotypes (p = 0.04) than other patients. Moreover, we showed that the CX(3)CR1- 280M allele was associated with higher peripheral CD4+ T cell counts not only in HIV+ patients but also in healthy controls (p = 0.003).
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PMID:Analysis of CCR5, CCR2, CX3CR1, and SDF1 polymorphisms in HIV-positive treated patients: impact on response to HAART and on peripheral T lymphocyte counts. 1647 97

The aim of this study was to determine the allele frequencies of genetic variants CCR5delta32, CCR2-64I, and SDF1-3'A (SDF1 801 A), which influence susceptibility to HIV-1 infection. We also investigated the effect of these variants on the general Ecuadoran population and on a group of HIV-infected individuals to determine the frequency of these genetics variants.
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PMID:CCR5delta32, CCR2-64I, and SDF1-3'A polymorphisms related to resistance to HIV-1 infection and disease in the Ecuadorian population. 1648 82

Among many factors that can influence vulnerability to infection and disease progression are genetic host factors together with the phenotype/genotype of the transmitting virus and the route of infection. Each of these factors alone or in combination could determine susceptibility to infection and subsequent rate of progression towards AIDS. Between host genetic factors identified and analyzed for their role in HIV-1 transmission and disease progression are polymorphisms in the genes encoding chemokine receptors and CCR5, CCR2 and SDF-1 a natural ligand for CXCR4 receptor. It has been shown that the distribution of this genetic polymorphisms and their role in the course of disease varies between different racial, ethnic and risk groups. The aim of present study was to examine the frequencies of polymorphic alleles CCR5-delta32, CCR2-64I and SDF-1-3'A and their role in human immunodeficiency virus (HIV-1) transmission in Polish population. The allelic and genotype distribution was studied in 103 HIV-1 infected patients (group HIV+) and 59 seronegative participants (group HIV-). Genotyping was done by the use of polymerase chain reaction with sequence-specific primers and restriction fragment length polymorphism. We found higher prevalence of CCR5-delta32 mutant allele among seronegative participants (13.6%) compared with HIV-infected patients (9.7%), although this did not attain statistical significance (p = 0.29). The CCR2-64I allelic frequency was almost identical in the HIV- and HIV+ groups (12.7% vs. 12.6%; respectively; p = 0.98). In contrast, the SDF-1-3'A allelic frequency was slightly lower among seronegative participants (15.3%) compared with HIV-infected patients (16.5%), and observed difference was not statistically significant (p = 0.77). Furthermore, we found that the genotype or allelic frequencies among HIV-1 infected patients were independent on the participant's sex, age at HIV-1 infection and the transmission route. Our results showed no significant differences in the prevalence of examined alleles and genotypes between HIV-1 infected patients and seronegative participants, which indicates that in the examined population they are not influencing host susceptibility to the HIV-1 infection.
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PMID:[Effects of CCR5-delta32, CCR2-64I and SDF-1-3'A polymorphic alleles on human immunodeficiency virus 1 (HIV-1) infection in the Polish population]. 1652 59


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