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 retrovirus 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, 1959Relationship between SIV and HIV is found

Origin

Earliest known infection occurred in Kinshasa, Zaire, 1959Relationship between SIV and HIV is foundOriginal transfer to humans is unknown

Transmission

Blood products

Transmission

Blood products Organ transplants

Transmission

Blood productsOrgan transplantsSexual intercourse

Transmission

Blood ProductsOrgan transplantsSexual intercourseVertical transmission

What is HIV?

Human Immunodeficiency Virus

What is HIV?

Human Immunodeficiency VirusA retrovirus

What is HIV?

Human Immunodeficiency VirusA retrovirusIt attacks T cells

What is HIV?

Human Immunodeficiency VirusA retrovirusIt attacks T cells Leads to opportunistic infection

What is HIV?

Human Immunodeficiency VirusA retrovirusIt attacks T cells Leads to opportunistic infectionProgresses to AIDS

What is AIDS?

Acquired Immunodeficiency Syndrome

What is AIDS?

Acquired Immunodeficiency SyndromeHIV infection confirmed

What is AIDS?

Acquired Immunodeficiency SyndromeHIV infection confirmedCD4 T-cell count is below 200

What is AIDS?

Acquired Immunodeficiency SyndromeHIV infection confirmedCD4 T-cell count is below 200 HIV related syndrome is present

The Impact of AIDSAge # 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

The Impact of AIDSRace or Ethnicity # of Cumulative AIDS Cases

White, not Hispanic 337,035

Black, not Hispanic 301,784

Hispanic 145,220

Asian/Pacific Islander 5,922

American Indian/Alaska Native 2,433

Race/ethnicity unknown 632

Disease Progression

What is a T- “helper” Cell?

The cell HIV targets

What is a T- “helper” Cell?

The cell HIV targetsImmune regulator cells

What is a T- “helper” Cell?

The cell HIV targetsImmune regulator cellsActivates 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 are 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 messagesServe as a docking device for viruses

Step 2: Entry

Virus breaches cell’s outer membrane

Step 2: Entry

Virus breaches cell’s outer membranePushes core of viral proteins inside cell body

Step 3: Uncoating

Viral core uncoats

Step 3: Uncoating

Viral core uncoatsReleases genetic material and enzymes

Step 4: Reverse Transcription

Reverse transcriptase processes viral genome

Step 4: Reverse Transcription

Reverse transcriptase processes viral genomeEnables virus to copy its genetic structure

Step 5: Nuclear Entry

The viral genome is transported to cell’s nucleus

Step 6: Integration

Viral DNA is completely “mixed into” host cell’s genome

Step 7: Transcription

Proviral DNA transcribes back into viral RNA

                                       

Step 7: Transcription

Proviral DNA transcribes back into viral RNAProduces 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 are assembledPackages of proteins migrate to cell’s surface

Step 9: Assembly

Cut proteins are assembledPackages of proteins migrate to cell’s surfaceBegin to bud from host cell

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.

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:

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 groupsCompared 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 enter 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 and 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.Heterozygous individuals had an extended life span while being infected for an average of 3 to 4 years

Immunity to HIV

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 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 siteChemotherapy 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 CCR5CCR2B and CCR3

Bad News

Other Chemokine receptors can compensate for the lack of CCR5CCR2B and CCR3It has not been proven that CCR5 drugs/therapies improve chances of vaccination, cure, or extended survival

Ethical Dilemmas

Employee/ Health Insurance Screenings

Ethical Dilemmas

Employee/ Health Insurance ScreeningsCCR5 Mutation gives false hope to some

Ethical Dilemmas

Employee/ Health Insurance ScreeningsCCR5 Mutation gives false hope to someStem cell usage for bone marrow therapy

Web Sites

http://critpath.org/aric/library/img005.htmhttp://tthhivclinic.com/lifecycle.htmhttp://www.sciam.com/0997issue/0997obrien.html

Thank You