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

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

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

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  1. Genetic Restriction of HIV-1 Infection and Progression to AIDS by a Deletion Allele of the CKR5 Structural Gene. Dean, M., M. Carrington, C. Winkler, G.A. Huttley, M.W. Smith, R. Allikmets, J.J. Goedert, S.P. Buchbinder, E. Vittinghoff, E. Gomperts, S. Donfield, D. Vlahov, R. Kaslow, A. Saah, C. Rinaldo, and R. Detels. 1996. Science 273 (5283):1856-1862. Wislaine Coby Seminar 475

  2. Introduction • Studies have shown the population are at risk of mortality from infectious agents due to inherited factors. • The HIV-1 plays a role in the study of host genetic variation and susceptibility to infection. • Specific alleles of the human lymphocyte antigen (HLA) locus has been associated with the progression from infection to an AIDS diagnosis.

  3. Chemokines • Chemokines bridge the communications gap between lymphocytes and other cells of the immune system. • The natural suppressors to the HIV- infection are chemokines RANTES, MIP-1x and MIP-1. • Fusin and CKR5 are chemokine receptors.

  4. Mapping of CKR genes

  5. Rationale • The fusin is mapped to chromosome 2q21. • The CKR5 gene is located in a cluster on chromosomes 3p21. • Gene-mapping is evidence of the occurrence of chemokine receptor genes in clusters of different regions of the human genome

  6. Genotypic markers and HIV-1 infection (G-Test)

  7. Rationale • Only the CKR5 had a significance in the distortion of genotype among the HIV-1 infected and non-infected.

  8. HIV-1 infected vs Non-infected • To examine the role of CKR5 in HIV-1 infected. • The two groups showed no difference in the allele frequency of CKR5. • Only a difference in the genotypic distribution between the two groups. • HIV-1 antibody-negative were among the homozygotes CKR5 32.

  9. Rationale behind the HIV-1 infected and Non-infected • A significance in the 32/ 32 genotype with the HIV-1 negative. • The CKR5 32 allele shows an association with the resistance to HIV-1 infection and antibody production.

  10. CKR5 32 genotypes with progression to AIDS • There were 1343 HIV-1 positive individuals. • Heterozygous vs Homozygous • No significant difference between rapid progression and the long-term progression in the hemophilia cohorts in the frequency of the +/32 genotype.

  11. Survival Analysis • Used the clinical 1992 AIDS definition to compare CKR5 genotypes (+/+ and +/32). • Results show the +/32 heterozygotes have a much slower progression to AIDS compared to +/+ homozygotes

  12. Conclusion • CKR5 is an important identification for HIV-1 infection. • The CKR532 allele does not affect susceptibility to infection but does postpone progression to AIDS in infected patients.

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