Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression

  title={Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression},
  author={Srinivas Mummidi and Seema S. Ahuja and Enrique Gonalez and Stephanie A. Anderson and Elvin N. Santiago and Kevin T. Stephan and Fiona E. Craig and Peter O’Connell and Victor Tryon and Robert A. Clark and Matthew J. Dolan and Sunil K Ahuja},
  journal={Nature Medicine},
Allelic variants for the HIV-1 co-receptors chemokine receptor 5 (CCR5) and CCR2, as well as the ligand for the co-receptor CXCR4, stromal-derived factor (SDF-1), have been associated with a delay in disease progression. We began this study to test whether polymorphisms in the CCRS regulatory regions influence the course of HIV-1 disease, as well as to examine the role of the previously identified allelic variants in 1,090 HIV-1 infected individuals. Here we describe the evolutionary… 
Global distribution of the CCR2-64I/CCR5-59653T HIV-1 disease-protective haplotype
The greater geographical distribution of the CCR2-64I/CCR5-59653T haplotype compared with that of CCR5-Δ32 suggests that it is a much older mutation whose origin predates the dispersal of modern humans.
Genetics of HIV-1 infection: chemokine receptor CCR5 polymorphism and its consequences.
The multiplicity of CCR5 genetic effects on HIV-1 disease underscores the critical importance of this gene in controlling AIDS pathogenesis and provides the logic for develop-ment of therapeutic strategies that target the interaction of HIV- 1 envelope and C CR5 in HIV-2 associated disease.
The effect of genetic variation in chemokines and their receptorson HIV transmission and progression to AIDS
Genetic ablation of AIDS progression by chemokine receptor and ligand gene variants has catalyzed development of novel therapies targeting the virus-co-receptor interaction.
Polymorphism of CCR5 affecting HIV disease progression in the Japanese population.
It is found that a CCR5 SNP and haplotype polymorphism affect HIV disease progression even in the Japanese population, indicating that the C CR5 genetic polymorphism affecting disease progression should be studied in a wider range of population.
Genetic Diversity within Chemokine Receptor 5 ( CCR 5
The results demonstrated the importance of genetic diversity in the CCR5 gene and clearly indicate the importance for understanding the pattern of genetic Diversity and its implications for better understanding AIDS.
Genetic acceleration of AIDS progression by a promoter variant of CCR5.
Genetic association analysis of five cohorts of people with acquired immunodeficiency syndrome (AIDS) revealed that infected individuals homozygous for a multisite haplotype of the CCR5 regulatory region containing the promoter allele, C CR5P1, progress to AIDS more rapidly than those with other CCR 5 promoter genotypes, particularly in the early years after infection.
Chemokine receptor polymorphisms and human immunodeficiency virus disease progression.
The role of polymorphisms in genes encoding chemokines and their receptors (CCR2B, SDF-1, and the promoter region of CCR5) in human immunodeficiency virus (HIV) disease progression was studied in 132
Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes.
It is demonstrated that the spectrum of CCR5 haplotypes associated with disease acceleration or retardation differs between African Americans and Caucasians, and there is a strong interactive effect between CCR 5 haplotypes with different evolutionary histories.
Association of chemokine receptor gene (CCR2-CCR5) haplotypes with acquisition and control of HIV-1 infection in Zambians
HIV-1 coreceptor gene haplotypes and diplotypes appear to modulate HIV-1 VL in seroconverters and alter the rate of HIV-2 acquisition by HESNs, and replicate or resemble findings reported in other African and European populations.


A chemokine receptor CCR2 allele delays HIV-1 disease progression and is associated with a CCR5 promoter mutation
CCR2-V64I is indeed protective against disease progression and is shown to be in complete linkage disequilibrium with a point mutation in the CCR5 regulatory region.
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.
Genetic association analysis of five acquired immunodeficiency syndrome (AIDS) cohorts revealed that although CCR2-64I exerts no influence on the incidence of HIV- 1 infection, HIV-1-infected individuals carrying the C CR2- 64I allele progressed to AIDS 2 to 4 years later than individuals homozygous for the common allele.
The role of CCR5 and CCR2 polymorphisms in HIV-1 transmission and disease progression
Entry of human immunodeficiency virus type 1 (HIV-1) into target cells requires both CD4 (ref. 1, 2) and one of a growing number of C-protein-coupled seven-transmembrane receptors3. Viruses
Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene
It is shown that a mutant allele of CCR-5 is present at a high frequency in caucasian populations, but is absent in black populations from Western and Central Africa and Japanese populations, and a 32-base-pair deletion within the coding region results in a frame shift, and generates a non-functional receptor that does not support membrane fusion or infection by macrophage- and dual-tropic HIV-1 strains.
Inherited Resistance to HIV-1 Conferred by an Inactivating Mutation in CC Chemokine Receptor 5: Studies in Populations with Contrasting Clinical Phenotypes, Defined Racial Background, and Quantified Risk
The data suggest that homozygous CCR5-2 is an HIV-1 resistance factor in Caucasians with complete penetrance, and that heterozygously CCR 5-2 slows the rate of disease progression in infected Caucasian homosexuals.
The role of a mutant CCR5 allele in HIV–1 transmission and disease progression
The CCR5 genotype of 1252 homosexual men enrolled in the Chicago component of the Multicenter AIDS Cohort Study (MACS) was analyzed and no evidence was found to suggest that heterozygotes were protected against HIV–1 infection, but a limited protective role against disease progression was noted.
Genetic polymorphism of CCR5 gene and HIV disease: The heterozygous (CCR5/Δccr5) genotype is neither essential nor sufficient for protection against disease progression
The results indicate that the CCR5/Δccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.
The role of viral phenotype and CCR-5 gene defects in HIV-1 transmission and disease progression
The protective effect of Δccr5 against disease progression is lost when the infecting virus uses CXCR-4 as a coreceptor, and a distinct survival advantage was shown for those with NSI virus.
Genetic Restriction of HIV-1 Infection and Progression to AIDS by a Deletion Allele of the CKR5 Structural Gene
The CKR5Δ32 deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.
Association between CCR5 Genotype and the Clinical Course of HIV-1 Infection
The role of CCR5 genotype alone and in relation to established progression markers in the clinical course of HIV-1 infection in participants from the Amsterdam Cohort Studies suggested a good estimation of the seroconversion date in the latter group.