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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 . (brief discussion of Figure. 2).

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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 (brief discussion of Figure. 2) Michael Dean, * Mary Carrington, * Cheryl Winkler, Gavin A. Huttley, Michael W. Smith, Rando Allikmets, James J. Goedert, Susan P. Buchbinder, Eric Vittinghoff, Edward Gomperts, Sharyne Donfield, David Vlahov, Richard Kaslow, Alfred Saah, Charles Rinaldo, Roger Detels, Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study, Stephen J. O'Brien Presented by Andrew Jackson

  2. What is CKR5? CKR5 (or CCR5) is a chemokine receptor protein which functions as a secondary receptor on CD4+ T lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1). Mutations in the CKR5 gene may prevent the CKR5 protein from being displayed and as such the HIV almost always fails to infect the lymphocyte.

  3. So… Are there any alterations in the CKR5 gene? Eight molecular genetic variants were identified by Dean et. al (1996). However only one mutation, a 32-base pair (bp) deletion (CKR5 Δ32 ) which causes a frame shift at amino acid 185 was significant. The CKR5 Δ32 occurred in approximately 10 % of study cohort, the other seven variants were found in less than 1% of the individuals studied .

  4. Does the frequency of mutated genes vary between HIV-1 infected and uninfected individuals? As is made evident in figure 2. only the CKR5 alleles (normal or wild type (+) and CKR532 deletion) displayed any significant differences between the genotypes (homozygous wild type, heterozygous and homozygous CKR532 deletion) among infected versus uninfected individuals (Dean et al., 1996)

  5. Upon investigating only the genotypic difference for the CCR5 gene between uninfected and infected HIV-1 individuals was determined to be of any significance Figure 2. from Science, Dean et al. 273 (5283): 1856 DIFFERENCES IN GENETIC PROFILE from Scientific American, Dean M. and O’’Brien S.J. September, 1997: 45-51  

  6. Conclusion The evidence suggests that the 32 base deletion in CKR5 gene may infer a form of resistance to HIV infection on the part of the host possibly by acting as a recessive restriction gene against HIV-1 infection (Dean et. al (1996).

  7. References Dean M., M.Carrington, * C.l 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.Genetic Restriction of HIV-1 Infection and Progression to AIDS by a Deletion Allele of the CKR5 Structural Gene. Science (5283):1856-1862. Dean M. and O’Brien S.J. 1997. In search of AIDS resistance genes. Scientific America, September 1997: 45-51.

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