CKR5 a Gene that can Protect Against AIDS

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CKR5 a Gene that can Protect Against AIDS

• Michael Kelsey

http//articles.health.msn.com/id/100064420
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Key Terms and Concepts

• HIV or Human Immunodeficiency Virus- destroys the
  human immune system and causes AIDS
• AIDS or Acquired Immunodeficiency Syndrome-
  reduction of CD4-helper T cells 20 or less,
  vulnerable to diseases
• Helper T Cells- CD4 chemokine receptor,
  recognizes antigens on the surface of a
  virus-infected cell and secretes lymphokines that
  stimulate B cells and killer T cells helper T
  cells are killed and destroyed by the AIDS virus

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The HIV virus attaches to helper T cells through
the CKR5 or Chemokine Receptor 5

• Chemokines- protein signals that activate and
  direct leukocytes and glycoproteins to move in a
  specific direction
• CKR5- a receptor for the chemokines RANTES, MIP-1
  alpha, and MIP-1 beta and a co-receptor on CD4
  helper T cells for HIV

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HIV has different attrations for cells depending
on the stage of infection

• M-Tropic- occurs in the early stage, the virus is
  attracted to macrophages
• Dual-Tropic- occurs in the middle phase, the
  virus infects both macrophages and T cells
• T-Tropic- occurs in the late phase, the virus has
  an affinity for T cells which begins the
  advancement of AIDS

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The CKR5 Gene

• Certain individuals were exposed to HIV and
  remained uninfected
• A mutation in a co-receptor could explain certain
  individuals being protected from HIV infection
• So, the chemokine receptor genes were mapped

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The CKR5 gene was identified by having a mutation
occurring in 10 of the individuals

• The chromosome corresponding to CKR5 displays a
  correlation between its mutation and HIV negative
  individuals

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CKR5 deletion mutation

• The mutation that was identified was a 32-base
  pair deletion which causes a frameshift
• Frameshift mutation- changes the amino acid
  sequence from the site of the mutation

http//ghr.nlm.nih.gov/dynamicImages/understandGen
etics/mutations_and_disorders/Frameshift.jpg
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CKR5 delta 32 homozygous allele cannot funtion as
a co-receptor for HIV or as a chemokine receptor

• Homozygous- having the same alleles at a
  particular gene locus on homologous chromosomes
• Allele- one of two alternate forms of a gene
  either dominant or recessive and are responsible
  for alternative traits
• Dominant- one allele is required to express the
  trait
• Recessive- two alleles are required to express
  the trait

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The CKR5 delta 32 allele was found to be recessive

• Only individuals with 2 copies of the mutant CKR5
  allele were found to have 100 immunity to the
  HIV virus

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CKR5 delta 32 genotype frequency

• Homosexuals with heterozygous CKR5 delta 32
  genotypes are more likely to be AIDS negative are
  significantly less likely to be AIDS positive
  after contracting HIV
• Heterozygous- containing both dominant and
  recessive alleles

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A Slowed Progression to AIDS

• Individuals characterized by not contracting AIDS
  after ten years are considered to have a slowed
  progression
• Individuals with the heterozygous CKR5 delta 32
  genotype display a significantly slowed
  progression of HIV

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Conclusions

• The CKR5 delta 32 gene mutation can slow
  progression or even prevent HIV by not allowing
  the virus to have a binding site on helper T
  cells
• These findings create new possibilities for the
  prevention and treatment of AIDS
• More research and funding is needed if a cure for
  AIDS is going to be found

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