1、CCR5 : and HIV Immunity,Gene Variation Works for and Against HIV Ashley Alexis & Hilda Hernandez,Background,1981: Homosexuals in New York and L.A.,Background,1981: Homosexuals in New York and L.A. 1983: New retrovirus is named HIV 1,Background,1981: Homosexuals in New York and L.A. 1983: New retrovi
2、rus is named HIV 1 1986: HIV 2 is isolated in West Africa,Origin,Earliest known infection occurred in Kinshasa, Zaire, 1959,Origin,Earliest known infection occurred in Kinshasa, Zaire, 1959 Relationship between SIV and HIV is found,Origin,Earliest known infection occurred in Kinshasa, Zaire, 1959 Re
3、lationship between SIV and HIV is found Original transfer to humans is unknown,Transmission,Blood products,Transmission,Blood products Organ transplants,Transmission,Blood products Organ transplants Sexual intercourse,Transmission,Blood Products Organ transplants Sexual intercourse Vertical transmis
4、sion,What is HIV?,Human Immunodeficiency Virus,What is HIV?,Human Immunodeficiency Virus A retrovirus,What is HIV?,Human Immunodeficiency Virus A retrovirus It attacks T cells,What is HIV?,Human Immunodeficiency Virus A retrovirus It attacks T cells Leads to opportunistic infection,What is HIV?,Huma
5、n Immunodeficiency Virus A retrovirus It attacks T cells Leads to opportunistic infection Progresses to AIDS,What is AIDS?,Acquired Immunodeficiency Syndrome,What is AIDS?,Acquired Immunodeficiency Syndrome HIV infection confirmed,What is AIDS?,Acquired Immunodeficiency Syndrome HIV infection confir
6、med CD4 T-cell count is below 200,What is AIDS?,Acquired Immunodeficiency Syndrome HIV infection confirmed CD4 T-cell count is below 200 HIV related syndrome is present,The Impact of AIDS,The Impact of AIDS,Disease Progression,What is a T- “helper” Cell?,The cell HIV targets,What is a T- “helper” Ce
7、ll?,The cell HIV targets Immune regulator cells,What is a T- “helper” Cell?,The cell HIV targets Immune regulator cells Activates B-cells,Structure of HIV,HIV Lifecycle,Step 1: Binding,The virus binds to host cell via receptors,What are Receptors?,Molecules that extend from the cell membrane,What ar
8、e Receptors?,Molecules that extend from the cell membrane Receive messages,What are Receptors?,Molecules that extend from the cell membrane Receive messages,What Are Receptors?,Molecules that extend from the cell membrane Receive messages Serve as a docking device for viruses,Step 2: Entry,Virus bre
9、aches cells outer membrane,Step 2: Entry,Virus breaches cells outer membrane Pushes core of viral proteins inside cell body,Step 3: Uncoating,Viral core uncoats,Step 3: Uncoating,Viral core uncoats Releases genetic material and enzymes,Step 4: Reverse Transcription,Reverse transcriptase processes vi
10、ral genome,Step 4: Reverse Transcription,Reverse transcriptase processes viral genome Enables virus to copy its genetic structure,Step 5: Nuclear Entry,The viral genome is transported to cells nucleus,Step 6: Integration,Viral DNA is completely “mixed into” host cells genome,Step 7: Transcription,Pr
11、oviral DNA transcribes back into viral RNA,Step 7: Transcription,Proviral DNA transcribes back into viral RNA Produces strands of viral proteins,Step 8: Translation,Protein strands are processed into chains of viral proteins,Step 9: Assembly,Cut proteins are assembled,Step 9: Assembly,Cut proteins a
12、re assembled Packages of proteins migrate to cells surface,Step 9: Assembly,Cut proteins are assembled Packages of proteins migrate to cells surface Begin to bud from host cell,CCR5 Genetic Mutation = HIV/AIDS Immunity!,N.C.I. team headed by Dr. Stephen J. OBrien conducted a study of 1,850 subjects
13、at high risk of HIV infection.,CCR5 Genetic Mutation = HIV/AIDS Immunity!,N.C.I. team headed by Dr. Stephen J. OBrien et al. conducted a study of 1,850 subjects at high risk of HIV infection. Separated subjects into two groups:,CCR5 Genetic Mutation = HIV/AIDS Immunity!,N.C.I. team headed by Dr. Ste
14、phen J. OBrien 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,RESULTS,Found that HIV could enter cells through CD4 receptors AND CCR5 receptors.,RESULTS,Found that HIV could e
15、nter cells through CD4 receptors AND CCR5 receptors. CCR5 receptor genes differed in patients,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 an
16、d was homozygous for the deletion CCR5 gene.,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. Hete
17、rozygous individuals had an extended life span while being infected for an average of 3 to 4 years,Immunity to HIV,HOMOZYGOUS,Cure Possibilities!,CCR5 proteins may help protect healthy people or delay the advance of AIDS,Cure Possibilities!,CCR5 proteins may help protect healthy people or delay the
18、advance of AIDS Genetic engineering can provide new genes that would stop CCR5 from serving as a docking site,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 C
19、hemotherapy and Bone Marrow transplants,Bad News,Other Chemokine receptors can compensate for the lack of CCR5,Bad News,Other Chemokine receptors can compensate for the lack of CCR5 CCR2B and CCR3,Bad News,Other Chemokine receptors can compensate for the lack of CCR5 CCR2B and CCR3 It has not been p
20、roven that CCR5 drugs/therapies improve chances of vaccination, cure, or extended survival,Ethical Dilemmas,Employee/ Health Insurance Screenings,Ethical Dilemmas,Employee/ Health Insurance Screenings CCR5 Mutation gives false hope to some,Ethical Dilemmas,Employee/ Health Insurance Screenings CCR5 Mutation gives false hope to some Stem cell usage for bone marrow therapy,Web Sites,http:/critpath.org/aric/library/img005.htm http:/ http:/ You,
