CCR5 genotype and plasma ß-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-1a, MIP-1ß 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-1a 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 (D32ccr5) in this population was 0.032; however, no D32ccr5 homozygote was detected. These results could be related to the intense ethnic admixture of the Brazilian population. There was no correlation between circulating ß-chemokines (MIP-1a, 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-1a than those observed in control samples (mean 31.20 pg/ml; P<0.05). Both HIV-1-infected and uninfected individuals heterozygous for the D32ccr5 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 ß-chemokine production may affect the immunopathogenesis of HIV-1.

CCR5-Δ32 genetic polymorphism associated with benign clinical course and magnetic resonance imaging findings in Brazilian patients with multiple sclerosis

“…Southern and Mediterranean Europeans (Portuguese, Italian and Middle Eastern), Asians, Arabians, Africans, and Native Amerindians have contributed to the formation of the present Brazilian population since the 16th century (49)(50). The results were also consistent with the first evidence for the contribution of the CCR5-Δ32 allele to the genetic background of the urban Brazilian population, which confirmed the intense ethnic admixture (45).…”

“…The frequencies of the heterozygote genotype among whites, blacks and browns were 14.0%, 8.0%, and 13.0%, respectively, and no homozygotes for the CCR5-Δ32 deletion were detected (48). These data contributed to the establishment of a scenario that shows a North-South gradient and are compatible with the colonization of Brazil, since the Southeastern and Southern regions received the highest numbers of European immigrants during the 19th and early 20th centuries (49)(50).…”

Stromal cell‐derived factor 1 (SDF1) genetic polymorphism in a sample of healthy individuals, seronegative individuals exposed to human immunodeficiency virus type 1 (HIV‐1) and patients infected with HIV‐1 from the Brazilian population

“…The overall allelic frequency of 0.1984 obtained can be explained by the heterogeneous ethnic structure of the Brazilian population. Southern and Mediterranean Europeans (Portuguese, Italian and Middle Eastern), Asians, Arabians, Africans, and native Amerindians contributed to the formation of the present Brazilian population since the 16th century (Mikawa et al ., 2002). The higher frequency of the SDF1‐3′A allele observed in Caucasian than in non‐Caucasian individuals (Mulattoes and Blacks were of African origin or descent) was in agreement with previous studies showing that SDF1‐3′A is infrequent among populations of African origin (Winkler et al ., 1998; Wang et al ., 2003).…”

Effects of single nucleotide polymorphisms in the RANTES promoter region in healthy and HIV‐infected indigenous Chinese*

“…RANTES can bind to the second extracellular loop of CCR5 and inhibit HIV‐1 infection of macrophages, possibly by competing with the virus for the receptor (Paxton et al ., 1996; Furci et al ., 1997). There is mounting evidence supporting the association of the in vivo level of RANTES expression with the course of HIV infection, but the relationship is complex and at best controversial (Cocchi et al ., 1995; Paxton et al ., 1996; Mikawa et al ., 2002). On the one hand, increased levels of RANTES expression by CD4 + T cells in highly exposed, uninfected individuals compared to blood donors suggest that RANTES might reduce HIV‐1 transmission (Cocchi et al ., 1995; Paxton et al ., 1996).…”