Genetic restriction of HIV1 and progression to AIDS by a deletion allele of the CKR5 structural gene

1
Genetic restriction of HIV-1 and progression to
AIDS by a deletion allele of the CKR5 structural
gene.
presented by Johann Campbell
Dean, M., 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, Hemophilia Growth and Development Study,
Multicenter AIDS Cohort Study,Multicenter
Hemophilia Cohort Study, San Francisco City
Cohort Study, ALIVE Study, OBrien, S. 1996.
Genetic Restriction of HIV-1 Infection and
Progression to AIDS by a Deletion Allele of the
CKR5 Structural Gene. Science 2731856-1861.
2
Can a cell receptor prevent HIV-1 infection?

• RANTES, MIP-1?, and MIP-1? suppress HIV-1
  infection
• Fusin, and CD4 enhance HIV-1 binding
• CKR5 also enhances binding of HIV-1
• Some CD4 individuals exposed to HIV-1 are
  uninfected
• Other cell receptors probably contributing to
  immunity

3
What is preventing exposed individuals from
contracting HIV?

• Examination of cohorts would reveal genetic
  differences
• Receptor hindrance probably found on the most
  differing gene
• Exposed but ve HIV-1 individual would most
  likely posses this difference
• Cohorts selected based on their high risk status

4
What is preventing exposed individuals from
contracting HIV?

• The gene that codes for fusin is found on
  chromosome 2p21
• CKR5 coding gene is found on chromosome 3p21

5
What is preventing exposed individuals from
contracting HIV?
6
CKR5 distortion also slows progression to AIDS

• Heterozygous individuals for CKR5?32 slow have a
  slower progression to AIDS
• Less binding sites for HIV-1 over time
• CKR5?32 appears to be dominant in its effects

7
How is CKR5?32 distributed among the population?
8
CKR5?32 deletion appears to confer immunity

• All homozygous CKR5?32 individuals were found to
  be HIV-1 ve
• Heterozygous CKR5?32 individuals progressed
  slower to AIDS
• CKR5?32 deletion appears to play a dominant role

9
Reference

• Dean, M., 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, Hemophilia Growth and Development Study,
  Multicenter AIDS Cohort Study,Multicenter
  Hemophilia Cohort Study, San Francisco City
  Cohort Study, ALIVE Study, OBrien, S. 1996.
  Genetic Restriction of HIV-1 Infection and
  Progression to AIDS by a Deletion Allele of the
  CKR5 Structural Gene. Science 2731856-1861.