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Genetic Restrictin of HIV-1 Infection and Progression to AIDS by a Deletion Allele of the CKR5 Structural Gene

Genetic Restrictin of HIV-1 Infection and Progression to AIDS by a Deletion Allele of the CKR5 Structural Gene. Jackie Medina 10-6-03 BIO 475-01. Introduction. Individuals in a population react differently to infectious diseases due to genetic factors

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Genetic Restrictin of HIV-1 Infection and Progression to AIDS by a Deletion Allele of the CKR5 Structural Gene

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  1. Genetic Restrictin of HIV-1 Infection and Progression to AIDS by a Deletion Allele of the CKR5 Structural Gene Jackie Medina 10-6-03 BIO 475-01

  2. Introduction • Individuals in a population react differently to infectious diseases due to genetic factors • Genetic factors leading to different reactions to HIV hard to reveal due to rapid rate of progression • Dean et. al wanted to find genetic factors leading to resistance to HIV-1 infection

  3. What are some molecules involved in HIV-1 infection and what are there roles? • RANTES- chemoattractant protein for peripheral blood monocytes. Inhibits HIV infection of T-cells • MIP-1 alpha and beta (Macrophage imflammatory protein-1) – Plays role in inflammatory response of blood monocytes • CKR5- Cysteine-Cysteine chemokine receptor – receptor for RANTES, MIP-1 alpha &beta, and macrophage tropic isolates of HIV-1.

  4. Where is the CKR5 locus? Technique used is Polymerase Chain Reaction (PCR) to develop a 90 radiation hybrid (RH) panel. The CKR5 locus was found on chromosome 3p21. Mappings provide evidence that C-C chemokine receptors occur in clusters.

  5. Are there alterations in CKR5? • 8 molecular variants were found in 600 individuals • 7 out of 8 variants occurred in </=1% of the group • A 32 base pair deletion of CKR5, causing a frame shift at amino acid 185, occurred in 10% of individuals. Variant is nonfunctional as receptor.

  6. What is the difference in allele distortion and frequency of the CKR5 variant involved in retroviral activities between HIV-1 infected and non-infected individuals? • 156 cell lines from Caucasion individuals were examined for distortion of allele and genotype frequency of CKR5 and other candidate genes • CKR5 was the only to show significant differences b/w the non-infected and infected

  7. What was the distribution of CKR5 32 base pair deletion alleles and genotypes among at HIV-1 risk individuals? • Risk groups include: hemophiliacs exposed to possibly contaminated blood, sexually active homosexuals, and intravenous drug users • Dramatic difference in CKR5 genotype distribution among the HIV exposed seronegative and HIV infected

  8. Continued • Homozygote Recessive genotypes were only found in the HIV negative, suggesting that this phenotype results in resistance • A number of heterozygote were found among the at risk groups • Heterozygotes correlated with a decreased rate of progression to AIDS from HIV-1

  9. Conclusion • CKR5 32 base pair deletion was found to be a genetic factor in resistance to HIV-1 • Heterozygotes show a slower rate of progression to AIDS • Hopefully this research and future research leads to a cure of this horrible disease

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