CCR5 genotypes and progression to HIV disease in perinatally infected children.
The CCR5 molecule, a chemokine receptor, is the most important co-receptor for macrophage-tropic HIV-1. A 32-bp deletion in the gene encoding CCR5 (CCR5-del32) confers nearly complete resistance to HIV-1 infection in homozygotes, and slows the rate of progression to AIDS in heterozygous adults. The aim of this study was to describe the CCR5 genotypes and the characteristics of HIV disease progression in perinatally infected children. From a total of 51 children analyzed for the CCR5-del32 mutation, 18 (35%) were considered to be rapid progressors, 28 (55%) were moderate progressors and 5 (10%) were slow progressors. A portion of the CCR5 gene was amplified by PCR from genomic DNA followed by agarose gel electrophoresis. Forty-nine children (96%) carried the homozygous wild type genotype for CCR5 while 2 (4%) carried the heterozygous wt/del32 genotype. In the population studied, the CCR5 genotype was unable to account for the differences in pattern of the disease progression among the three groups (rapid, moderate and slow progressors), and the allele frequency of CCR5-del32 was too low to allow statistical comparisons with adequate resolving power. Studies on larger populations may help to further elucidate the role of this allele and other host factors in the regulation of HIV-1 pathogenesis in children.
de Angelis
Daniela Souza Araújo
DS
Institute of Tropical Medicine of São Paulo, HCFM, University of São Paulo, Avenida Dr. Enéas de Carvalho Aguiar 470, 04503-000 São Paulo (SP), Brazil. angelis@usp.br
Freire
Wilton Santos
WS
Pannuti
Cláudio Sergio
CS
Succi
Regina Célia de Menezes
RC
Machado
Daisy Maria
DM
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004587:Electrophoresis, Agar Gel; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5 / Q000235:genetics*
D019713:Receptors, CCR5