Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study.
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.
Viraemia and p24 antigenaemia are independent risk factors for the emergency of a zidovudine-resistant genotype in nucleoside analogue-treated HIV-1 infection.
We found that (i) the prevalence of the common variant MBL alleles is correlated with the incidence of tuberculosis in sub-Saharan Africa (r=0.565), (ii) the mutant MBLG57E allele, in either the homozygous or compound heterozygous state, is associated with susceptibility to HIV-1 infection in the Gabonese population (P=0.019).Our data plus those in the literature suggest that individuals who are homozygous for the mutant MBL alleles display increased susceptibility to infections.
This study provides the first evidence for SDF-3'A polymorphism in resistance to HIV-1 infection in Thais, and may represent the resistant mechanism in the extremely rare CCR5-Delta32 mutant of other ethnic groups such as Africans and Japanese.
In vitro HIV-1 infection assays with CCR5-using primary isolates demonstrated that thymocytes with the heterozygous CCR5 Delta 32 mutation produced less p24 than did CCR5 wild-type thymocytes.
This study provides an effective approach to create a CXCR4 mutation with HIV-1 infection inhibition function and without leaving any genetic footprint inside cells, thereby shedding light on an application in HIV-1 gene therapy and avoiding side effects caused by deficiency or destruction of CXCR4 function.
The CC-chemokine receptor CCR5 has been shown to be the major coreceptor for HIV-1 entry into cells, and humans with homozygous mutation in the ccr5 gene are highly resistant to HIV-1 infection, despite the existence of many other HIV-1 coreceptors.
Our findings indicate that homozygosity for the codon 54-allele associated with low MBL production in the exon-1 of the MBL-2 gene is associated with increased susceptibility to HIV-1 infection in the studied population.
Genetic findings have yielded major insights into the in vivo roles of individual coreceptors and their ligands; of particular importance is the discovery of an inactivating mutation in the CCR5 gene which, in homozygous form, confers strong resistance to HIV-1 infection.
In vitro HIV-1 infection assays with CCR5-using primary isolates demonstrated that thymocytes with the heterozygous CCR5 Delta 32 mutation produced less p24 than did CCR5 wild-type thymocytes.
Besides, we found the significant epistatic effects between the CCR5 58755-A/G and CCR5 59029-A/G polymorphisms associated with the lower risk of HIV-1 infection.
Here, we determined the association of the CCR5 promoter SNPs, the CCR5-Δ32 mutation, CCR2-V64I SNP, and HH frequencies with resistance/susceptibility to HIV-1 infection in a cohort of HIV-1-serodiscordant couples from Colombia.
However, the low frequency of CCR5-Delta32 homozygosity observed among HIV-1-exposed seronegative individuals shows that the allele could not explain, by itself, the natural resistance to HIV-1 infection and different mechanisms of protection against HIV-1 infection that must be involved in this population.
These findings suggest strongly that diversity in addition to sequence specificity at HLA-A and -B loci can influence the rate of disease progression following HIV-1 infection.
Previous research has proven that disruption of either the CCR5 or the CXCR4 gene confers resistance to R5-tropic or X4-tropic human immunodeficiency virus type 1 (HIV-1) infection, respectively.