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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. Presented by Jaime Elvin

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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 Presented by Jaime Elvin Dean, R., M. Carrington, C. Winkler, G. Huttley, M. Smith, R. Allikmets, J. Goedert, S. Buchbinder, E. Vittinghoff, E. Gomperts, S. Donfield, D.Vlahov, R. Kaslow, A. Saah, C. Rinaldo, R. Detels, and S. O’Brien. 1996. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 273:1856-1862.

  2. Background • Genetically linked traits • HIV population • Seronegative at risk individuals and seropositive individuals • The people that were used were hemophiliacs, IV drug users, and the gay population

  3. Chemokine Receptors • Chemokine receptors • CKR5 • RANTES • MIP 1

  4. Techniques • PCR (Polymerase Chain Reaction) • Combined single-stranded conformation polymorphism-heteroduplex analysis approach which just happens to be sensitive to a point mutation • polymorphism is is the occurrence of three or more distinct types of adults in a species.

  5. Rational • Mutation in CKR5/delta 32 • 32 base pair deletion • found in about 10 % of the population • nonfunctional as a chemokine receptor and a coreceptor

  6. Rational • 156 cell lines were evaluated • 170 loci which play a role in pathogenesis and infection • CKR5 was found to be the only significant varation

  7. Genotypic markers 37 and HIV-1 infection (G test)

  8. CKR5 role in immunity • evaluated CKR5 from 6 cohort • CKR5 delta 32 were only found in seronegative individuals • CKR5 and CKR5 delta 32 were found in both seropositive and seronegative populations

  9. Conclusion • CKR5 can be linked to HIV-1 immunity • difference in the homosexual and hemophilic population in their disease progression • homosexual cohorts heterozygous for the CKR5 delta 32 deletion showed a decrease in disease progression

  10. Future plans • The effects on the homosexual population and the hemophilic population • The mode of transmission and amount of the virus transmitted upon infection were the most reasonable explanations • Further studies are needed to explain these differences before the heterozygous conditions can truly be said to confer a protective effect

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