Interpretation of data, Figure 2, and Table two from Dean et al (1996) article.

1. Interpretation of data, Figure 2, and Table two from Dean et al (1996) article. 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, R. Detels. 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 on HIV’s Genetic Diversity • Human immunodeficiency virus is an RNA virus in which the degree of genetic variation observed is phenomenal. • This means that that inherited factors influence the risk of mortality from infectious agents (Hobson 1993).

3. CD4+ and HIV • CD4+ cells are critical in managing immune responses and when they are depleted, immune defenses are weakened. • When HIV and other pathogens enter the body, CD4+ cells, operating through a network of chemical interactions, instruct other cells to disable the invading organisms. • HIV actually attaches to the CD4 protein on the surface of the cells to gain entry. • New Experiments suggest that the CD4 protein alone is not enough to allow viral entry into cells. Scientists believe they have now identified a second doorway that the virus needs to open to infect a cell

4. CKR5 as aCo- Receptor for HIV entry Gain • Chemokine receptor 5 (CKR5) protein serves as a secondary receptor on CD4+ lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1).

5. Genotype Frequency Figure 2

6. Conclusion • With the exception of CKR5, none of the loci tested displayed a significant distortion of genotype frequencies among the infected versus uninfected individuals (Dean et al 1996).

7. Figure 1

8. Heterozygote Recessive CKR5 Delta 32 deletion allele.

9. Recessive Phenotype for the CKR5 32 deletion Allele.

10. Conclusion of defective CKR-5 allele • Homozygous individuals appear to have inherited a defective CKR-5 allele that contains an internal 32 base pair deletion. • The encoded protein (internal 32 base pair) cannot be detected at the cell surface. The 32-base pair deletion within the coding region results in a frame shift and generates a non-functional receptor that does not support membrane fusion or infection by macrophage and dual tropic HIV-1 strains (Samson 1996). • The CKR-5 allele present in the human population appears to protect homozygous individuals from sexual transmission of HIV-1. • These findings indicate the importance of CKR-5 in HIV-1 transmission and suggest that targeting the HIV-1-CKR-5 interaction may provide a means of preventing or slowing disease progression (Liu et al 1996).

11. Can The CKR5 deletion 32 allele gain immunity response? • Further studies of homozygous 32/32 individuals to determine whether they have a memory T cell response to the virus, which would indicate that they were infected and mounted a successful immune response, would be enlightening. • It is not possible for 32/32 individuals to become infected by certain strains of HIV-1 and gain immunity, Because observed 32/32, HIV-1-seronegative individuals in homosexual, hemophiliac, and intravenous drug-use cohorts have this genotype that confers broad protection against infection (Samson 1996).

12. References