2. CCR5 : and HIV Immunity Gene Variation Works for and Against HIV Ashley Alexis & Hilda Hernandez

3. Background 1981: Homosexuals in New York and L.A.

4. Background 1981: Homosexuals in New York and L.A. 1983: New retrovirus is named HIV 1

5. Background 1981: Homosexuals in New York and L.A. 1983: New retrovirus is named HIV 1 1986: HIV 2 is isolated in West Africa

6. Origin Earliest known infection occurred in Kinshasa, Zaire, 1959

7. Origin Earliest known infection occurred in Kinshasa, Zaire, 1959 Relationship between SIV and HIV is found

8. Origin Earliest known infection occurred in Kinshasa, Zaire, 1959 Relationship between SIV and HIV is found Original transfer to humans is unknown

9. Transmission Blood products

10. Transmission Blood products Organ transplants

11. Transmission Blood products Organ transplants Sexual intercourse

12. Transmission Blood Products Organ transplants Sexual intercourse Vertical transmission

13. What is HIV? Human Immunodeficiency Virus

14. What is HIV? Human Immunodeficiency Virus A retrovirus

15. What is HIV? Human Immunodeficiency Virus A retrovirus It attacks T cells

16. What is HIV? Human Immunodeficiency Virus A retrovirus It attacks T cells Leads to opportunistic infection

17. What is HIV? Human Immunodeficiency Virus A retrovirus It attacks T cells Leads to opportunistic infection Progresses to AIDS

18. What is AIDS? Acquired Immunodeficiency Syndrome

19. What is AIDS? Acquired Immunodeficiency Syndrome HIV infection confirmed

20. What is AIDS? Acquired Immunodeficiency Syndrome HIV infection confirmed CD4 T-cell count is below 200

21. What is AIDS? Acquired Immunodeficiency Syndrome HIV infection confirmed CD4 T-cell count is below 200 HIV related syndrome is present

22. The Impact of AIDS Age# of Cumulative AIDS Cases Under 5:6,928 Ages 5 to 12:2,066 Ages 13 to 19:4,219 Ages 20 to 24:27,880 Ages 25 to 29:103,085 Ages 30 to 34:175,343 Ages 35 to 39:177,759 Ages 40 to 44:131,718 Ages 45 to 49:77,152 Ages 50 to 54:40,972 Ages 55 to 59:22,423 Ages 60 to 64:12,415 Ages 65 or older:11,065

23. The Impact of AIDS Race or Ethnicity# of Cumulative AIDS Cases White, not Hispanic337,035 Black, not Hispanic301,784 Hispanic145,220 Asian/Pacific Islander5,922 American Indian/Alaska Native2,433 Race/ethnicity unknown632

24. Disease Progression

25. What is a T- “helper” Cell? The cell HIV targets

26. What is a T- “helper” Cell? The cell HIV targets Immune regulator cells

27. What is a T- “helper” Cell? The cell HIV targets Immune regulator cells Activates B-cells

28. Structure of HIV

29. HIV Lifecycle

30. Step 1: Binding The virus binds to host cell via receptors

31. What are Receptors? Molecules that extend from the cell membrane

32. What are Receptors? Molecules that extend from the cell membrane Receive messages

33. What are Receptors? Molecules that extend from the cell membrane Receive messages

34. What Are Receptors? Molecules that extend from the cell membrane Receive messages Serve as a docking device for viruses

35. Step 2: Entry Virus breaches cell’s outer membrane

36. Step 2: Entry Virus breaches cell’s outer membrane Pushes core of viral proteins inside cell body

37. Step 3: Uncoating Viral core uncoats

38. Step 3: Uncoating Viral core uncoats Releases genetic material and enzymes

39. Step 4: Reverse Transcription Reverse transcriptase processes viral genome

40. Step 4: Reverse Transcription Reverse transcriptase processes viral genome Enables virus to copy its genetic structure

41. Step 5: Nuclear Entry The viral genome is transported to cell’s nucleus

42. Step 6: Integration Viral DNA is completely “mixed into” host cell’s genome

43. Step 7: Transcription Proviral DNA transcribes back into viral RNA

44. Step 7: Transcription Proviral DNA transcribes back into viral RNA Produces strands of viral proteins

45. Step 8: Translation Protein strands are processed into chains of viral proteins

46. Step 9: Assembly Cut proteins are assembled

47. Step 9: Assembly Cut proteins are assembled Packages of proteins migrate to cell’s surface

48. Step 9: Assembly Cut proteins are assembled Packages of proteins migrate to cell’s surface Begin to bud from host cell

49. CCR5 Genetic Mutation = HIV/AIDS Immunity! N.C.I. team headed by Dr. Stephen J. O’Brien conducted a study of 1,850 subjects at high risk of HIV infection.

50. CCR5 Genetic Mutation = HIV/AIDS Immunity! N.C.I. team headed by Dr. Stephen J. O’Brien et al. conducted a study of 1,850 subjects at high risk of HIV infection. Separated subjects into two groups:

51. CCR5 Genetic Mutation = HIV/AIDS Immunity! N.C.I. team headed by Dr. Stephen J. O’Brien et al. conducted a study of 1,850 subjects at high risk of HIV infection. Separated subjects into two groups Compared how often allele combinations showed up in each group

52. RESULTS Found that HIV could enter cells through CD4 receptors AND CCR5 receptors.

53. RESULTS Found that HIV could enter cells through CD4 receptors AND CCR5 receptors. CCR5 receptor genes differed in patients

54. RESULTS Found that HIV could enter cells through CD4 receptors AND CCR5 receptors. CCR5 receptor genes differed in patients 1 out of every 5 (3%) of the resistant individuals carried the genetic mutation and was homozygous for the deletion CCR5 gene.

55. RESULTS Found that HIV could enter cells through CD4 receptors AND CCR5 receptors. CCR5 receptor genes differed in patients 1 out of every 5 (3%) of the resistant individuals carried the genetic mutation and was homozygous for the deletion CCR5 gene. Heterozygous individuals had an extended life span while being infected for an average of 3 to 4 years

56. Immunity to HIV

57. Cure Possibilities! CCR5 proteins may help protect healthy people or delay the advance of AIDS

58. Cure Possibilities! CCR5 proteins may help protect healthy people or delay the advance of AIDS Genetic engineering can provide new genes that would stop CCR5 from serving as a docking site

59. Cure Possibilities! CCR5 proteins may help protect healthy people or delay the advance of AIDS Genetic engineering can provide new genes that would stop CCR5 form serving as a docking site Chemotherapy and Bone Marrow transplants

60. Bad News Other Chemokine receptors can compensate for the lack of CCR5

61. Bad News Other Chemokine receptors can compensate for the lack of CCR5 CCR2B and CCR3

62. Bad News Other Chemokine receptors can compensate for the lack of CCR5 CCR2B and CCR3 It has not been proven that CCR5 drugs/therapies improve chances of vaccination, cure, or extended survival

63. Ethical Dilemmas Employee/ Health Insurance Screenings

64. Ethical Dilemmas Employee/ Health Insurance Screenings CCR5 Mutation gives false hope to some

65. Ethical Dilemmas Employee/ Health Insurance Screenings CCR5 Mutation gives false hope to some Stem cell usage for bone marrow therapy

66. Web Sites http://critpath.org/aric/library/img005.h tm http://tthhivclinic.com/lifecycle.htm http://www.sciam.com/0997issue/0997 obrien.html

67. Thank You