CCR5-DELTA 32

Mekko Jean Bacorro

Liceo de Cagayan
University
 WHAT IS CCR5?
CC Chemokine Receptor 5
Part of the G- Protein Chemokine Receptor Family
that helps release calcium and inositol triphosphate

Chemokine- Small proteins that

functions as:
 Immune Surveillance
 Immune cell recruitment
 WHAT IS CCR5?
CC Chemokine Receptor 5
Found in macrophages, dendritic cells,
memory T-cells

• Endothelium, epithelium, vascular

smooth muscles and neuroglia

Macrophage Astrocytes
Epithelium
CCR5 as co-receptor
1996- Discovered that CCR5 is necessary as a
co-receptor for the entry of macrophage
tropic HIV strains

The virus uses this receptor for initial infection

to the host cell
HIV-CCR5 CD8+ cells are suppressor (cytotoxic) T-cells
that helps in Antigen Recognition

• During inflammation, the level of CCR5

expression is up-regulated in CD8+ cells,
enhancing the adaptive immune response
CD4+
01 Attachment

CD8+ Antigen
CD4+ cells are found in the cell surface of host
cell as helper/inducer T-cell. CCR5 helps Recognition 02
stimulate these cells to release cytokines and is
where the entry of HIV strain occurs.

•IMPORTANT FACTOR in HIV infection Phase 1

CCR5-DELTA 32

1996- Genetic
mutation in
Chromosome
3p21.31
 CCR5-DELTA 32
Analysis of ORF revealed deletion of
32 base pairs consisting of nucleotides
794 to 825
•Deletion involves frameshift
Localized in the short arm of mutation
chromosome 3 at position 21.21 215 Amino Acids
× last three transmembrane domains

Genetic A
n as well as regions important in G-

some
iOr g i protein interaction/signal transduction

Chromo
s nalysi
Tandem repeats found in coding
× Black Plague region of the CCR5 gene could
× Small Pox cause homologous recombination
 Gene Frequencies
Azhkenazi Jews Middle East
20.93% 2-5%

Indian
1%
European Descent
10%
Understanding the Mechanism of
CCR5 ∆32
• Found in the endoplasmic reticulum, exerts trans-dominant negative e ect on wild type CCR5 inhibiting it’s transport to
the cell surface

Protective E ect
of ∆32 mutation
 Physiological
Manifestations
• Individuals homozygous for ∆32 which abolishes CCR5 receptor are healthy and at no apparent
disadvantage

Rheumatoid Athritis Renal Allograft CAD/MI

Provides protection from Lowers the In Cardiovascular
inflammatory process percentage of Disease and
transplantation Myocardial
rejection Infarction, it lowers
TAG and increases
HDL, resulting in
better lipid profile

Liver Disease
Brain Injury
Bone Repair
Yellow fever
Tickborne
Encephalitis
 Cured from HIV
Timothy Ray
Brown
March, 2019 London
Berlin patient
• HIV free for about 18 months up
to present Germany
• Stem cell donor has the mutant • Cured after receiving Bone
allele Marrow Transplant from donor
who possess the homozygous
delta 32
• 3-full months of being HIV
negative
Breakthrough News
 Antiretroviral Drugs

MARAVIROC (Pfizer)
40% 80% 60% 50% Has small molecules of CCR5
receptor
2007
Future Researchers still continue to test the
ARVs to lower its toxicity for the patients

Gene Therapy
An on going process of finding default genes
or altering genes to completely eliminate the
virus
Thank You