Exercise your brain!

Activity 7C: AIDS

Group 6:
Shelly Tan A19SC0378

Sharon Chan Xi Ying A19SC0377

Siti Zafirah Binti Ali A19SC0398

Tan Xin Yun A19SC0412

1. Point out the target cell(s) and gene(s) of HIV patients.

- Target cells: white blood cells → CD4+ T cells (major), macrophages, and dendritic cells.

- Genes: CD4+ T cells bind to CD4 receptors on the cell surface but it requires
co-receptor such as CCR5 or CXCR4 to enter the cell. The specific gene associated with
these 2 co-receptors is the CCR5 gene and CXCR4 gene for CCR5 and CXCR4
receptors respectively.

2. Using a table, compare the standard of care treatment for HIV patients and gene therapeutic
options

Standard care Gene therapy

Treatment Antiretroviral treatment (ART) Suicide gene therapy

Knockout gene therapy

Aim - controls viral replication - Cure AIDS

- enhances and maintains - Long-term suppression of
immunologic function viral replication
- decreases clinical morbidity and - Restoration of immune
mortality (provides a normal life function
expectancy) - Reduction of transmission
risk.

Administration Three-drug oral daily regimen Viral vectors

- 2 nucleoside analogue reverse Non viral vectors
transcriptase inhibitors (NRTIs)
- integrase inhibitor/ NNRTIs/
protease inhibitor

Mechanism - Reverse transcriptase inhibitors Suicide gene therapy:

 prevent virus from replicating - Transduce suicide
- integrase inhibitor prevents viral gene gene into target cells,
integration convert prodrug into
- Protease inhibitor: prevents cleavage cytotoxic substance
of viral polyprotein precursors into Knockout gene therapy:
mature, functional proteins for viral - CCR5 can sometimes
replication pass its role to
CXCR4
- Delete CCR5 gene

3. What is the connection between the HIV life cycle and HIV medicines?

The connection between HIV life cycle and HIV medicines is the type of treatment available on
different stages of the HIV life cycle and how it works in each of these stages. HIV medicines
help in protecting the immune system by using drugs that block the replication machinery of the
HIV virus.
Examples of some methods that can be used to stop HIV at different stages in the HIV life cycle.
● Binding stage:
○ CCR5 receptor, which is the primary co-receptor that is used by HIV to infect
immune cells.
○ Thus, CCR5-blocking drugs and post-attachment inhibitors such as maraviroc
are used to prevent the binding of HIV to CD4+ T cells.
● Fusion stage:
○ Fusion inhibitors can be used to stop the fusion of HIV envelope and CD4
membrane.
● Reverse transcription:
○ Non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse
transcriptase inhibitors (NRTIs) are used to prevent the reverse transcription of
HIV RNA to DNA in CD4+ T cells.
4. AIDS is not a genetic disease. However, gene therapy could be a significant mode of
treatment among AIDS patients. Illustrate (flow diagram) a possible gene therapy for
HIVpatients.

Collecting CD8+ T cell from HIV patient (a), inserting CAR genes into CD8+ T cells in vitro (b),
expansion and functional identification of CAR T cells (c), reinfusing the HIV-specific CAR T
cells into patients (d), and CAR T cells killing HIV-infected cells (e).