Distribution of Chemokine Receptor CCR2 and CCR5 Genotypes and Their Relative Contribution to Human Immunodeficiency Virus Type 1 (HIV-1) Seroconversion, Early HIV-1 RNA Concentration in Plasma, and Later Disease Progression
AUTOR(ES)
Tang, Jianming
FONTE
American Society for Microbiology
RESUMO
At the CC (β) chemokine receptor 2 (CCR2) and CCR5 loci, combinations of common single-nucleotide polymorphisms (SNPs) and a 32-bp deletion (Δ32) form nine stable haplotypes (designated A through G*2). The distribution of these CCR2-CCR5 haplotypes was examined among 703 participants in the Multicenter AIDS Cohort Study (MACS), the District of Columbia Gay (DCG) Study, and the San Francisco Men’s Health Study (SFMHS). Highly exposed and persistently seronegative (HEPS; n = 90) Caucasian men from MACS more frequently carried heterozygous G*2 (Δ32) genotypes (especially A/G*2) and less frequently carried the homozygous E/E genotype compared with 469 Caucasian seroconverters (SCs) from the same cohort (P = 0.004 to 0.042). Among 341 MACS Caucasian SCs with 6- to 12-month human immunodeficiency virus type 1 (HIV-1) seroconversion intervals and no potent antiretroviral therapy, mean plasma HIV-1 RNA level during the initial 42 months after seroconversion was higher in carriers of the E/E genotype and lower in those with the 64I-bearing haplotype F*2 or the Δ32-bearing haplotype G*2 (and especially genotypes A/G*2 and F*2/G*2). A multivariable model containing these CCR markers showed significant composite effects on HIV-1 RNA at each of four postconversion intervals (P = 0.0004 to 0.050). In other models using time to AIDS as the endpoint, the same markers showed more modest contributions (P = 0.08 to 0.24) to differential outcome during 11.5 years of follow-up. Broadly consistent findings in the larger MACS Caucasian SCs and the smaller groups of MACS African-American SCs and the DCG and SFMHS Caucasian SCs indicate that specific CCR2-CCR5 haplotypes or genotypes mediate initial acquisition of HIV-1 infection, early host-virus equilibration, and subsequent pathogenesis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=136835Documentos Relacionados
- CCR5 genotype and plasma ß-chemokine concentration of Brazilian HIV-infected individuals
- Frequency of polymorphisms of genes coding for HIV-1 co-receptors CCR5 and CCR2 in a Brazilian population
- CCR5 genotypes and progression to HIV disease in perinatally infected children
- The amino-terminal domain of the CCR2 chemokine receptor acts as coreceptor for HIV-1 infection.
- HIV-1 infection through the CCR5 receptor is blocked by receptor dimerization