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, 1959
Relationship between SIV and HIV is
found
Origin
Earliest known infection occurred in
Kinshasa, Zaire, 1959
Relationship 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 transmission
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?
Human 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 confirmed
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
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
The Impact of AIDS
Race 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 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 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 messages
Serve as a docking
device for viruses
Step 2: Entry
Virus breaches
cell’s outer
membrane
Step 2: Entry
Virus breaches
cell’s 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 viral
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 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 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 are
assembled
Packages of proteins
migrate to cell’s
surface
Step 9: Assembly
Cut proteins are
assembled
Packages of proteins
migrate to cell’s
surface
Begin 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 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 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 site
Chemotherapy 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 proven 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.h
tm
http://tthhivclinic.com/lifecycle.htm
http://www.sciam.com/0997issue/0997
obrien.html
Thank You