title: CCR5 genotype and plasma beta-chemokine concentration of Brazilian HIV-infected individuals.
abstract: The 32-bp deletion in the HIV-1 co-receptor CCR5 confers a high degree of resistance to HIV-1 infection in homozygous individuals for the deleted allele and partial protection against HIV-1 during disease progression in heterozygotes. Natural ligands for CCR5, MIP-1alpha, MIP-1beta and RANTES, have been shown to inhibit HIV replication in CD4+ T cells. In the present study, we examined the CCR5 genotype by PCR and the plasma levels of RANTES and MIP-1alpha by ELISA among blood donors (N = 26) and among HIV-1-infected individuals (N = 129). The control group consisted of healthy adult volunteers and HIV-1-infected subjects were an asymptomatic and heterogeneous group of individuals with regard to immunologic and virologic markers of HIV-1 disease. The frequency of the CCR5 mutant allele (Delta32ccr5) in this population was 0.032; however, no Delta32ccr5 homozygote was detected. These results could be related to the intense ethnic admixture of the Brazilian population. There was no correlation between circulating beta-chemokines (MIP-1alpha, RANTES) and viral load in HIV-infected individuals. RANTES concentrations in plasma samples from HIV+ patients carrying the homozygous CCR5 allele (CCR5/CCR5) (28.23 ng/ml) were higher than in the control samples (16.07 ng/ml; P<0.05); however, this HIV+ patient group (mean 26.23 pg/ml) had significantly lower concentrations of MIP-1alpha than those observed in control samples (mean 31.20 pg/ml; P<0.05). Both HIV-1-infected and uninfected individuals heterozygous for the Delta32ccr5 allele had significantly lower concentrations of circulating RANTES (mean 16.07 and 6.11 ng/ml, respectively) than CCR5/CCR5 individuals (mean 28.23 and 16.07 ng/ml, respectively; P<0.05). These findings suggest that the CCR5 allele and beta-chemokine production may affect the immunopathogenesis of HIV-1.
authors.affiliation: Pós-Graduação em Biotecnologia, Instituto de Química, Universidade Estadual Paulista, Araraquara, SP, Brasil. costapi@fcfar.unesp.br
authors.forename: A Y
authors.initials: AY
authors.lastname: Mikawa
authors.forename: S A
authors.initials: SA
authors.lastname: Tagliavini
authors.forename: P I
authors.initials: PI
authors.lastname: Costa
mesh_terms: D000328:Adult; D000483:Alleles; D001782:Blood Donors; D016022:Case-Control Studies; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D015658:HIV Infections / Q000097:blood* / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000097:blood*; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5 / Q000235:genetics*; D019562:Viral Load
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5