SSCG 4723

Exercise Yr Brain Activity: 7C_AIDS

Group 3
Leong Mei Xin - A19SC0140
Lim Guan Yang - A19SC0142
Nurin Asfa Baqiyah - A19SC0306
Ku Shin Yu - A19SC0131
Edelweis Salwa Balqis - A19SC9049

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

- Target cell(s) of HIV patients:
- CD4+T cell (a type of white blood cell involved in the immune response)
- HIV specifically targets and infects CD4+T cells, leading to the depletion and
weakening of immune system
- Gene(s) of HIV patients:
- CCR5 gene and CXCR4 gene
- HIV infects cells by binding to the CD4 receptor on the cell surface and then
entering the cell through co-receptors (eg: CCR5 & CXCR4)
- Genes (eg: CCR5 & CXCR4 genes) encoding the receptors play a role in
determining the susceptibility and progression of HIV infection

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

Standard of care treatment for HIV Gene Editing

Antiretroviral therapy (ART) : combination of Techniques like CRISPR-Cas9 are being

HIV medicine called HIV treatment regimen explored to modify the genetic material of
(consisting of two nucleoside analogue HIV-infected cells. This approach aims to
reverse transcriptase inhibitors combined with disrupt the viral DNA integrated into the host
a third drug, either an integrase inhibitor, a cell's genome, potentially rendering the virus
non-nucleoside reverse transcriptase inhibitor, inactive.
or a protease inhibitor).
- It will attack the infection-fighting
CD4 cells (CD4 T lymphocyte) of
immune system.
- Prevent HIV from multiplying.
- Reduce HIV transmission
3. What is the connection between the HIV life cycle and HIV medicines?
Antiretroviral therapy (ART) involves the use of a combination of HIV medicine to treat HIV
infection. In ART, there are seven drug classes designed to target specific steps/stages in the
HIV life cycle which are able to effectively prevent HIV from multiplying and advancing to AIDS.

Stage HIV Life Cycle HIV medicine

1 Binding (a.k.a Attachment) of HIV to ● CCR5 Antagonist

CD4 cell’s receptor ● Post-attachment inhibitors

2 Fusion of HIV envelope and CD4 cell ● Fusion Inhibitors

membrane

3 Reverse Transcription of HIV RNA ● Non-nucleoside reverse transcriptase

to DNA inside CD4 cell inhibitors (NNRTIs)
● Nucleoside reverse transcriptase
inhibitors (NRTIs)

4 Integration of HIV DNA into DNA of ● Integrase inhibitors

the CD4 cell

5 Replication of HIV component (e.g. N/A

long protein chain) using CD4 cell
machinery

6 Assembly of HIV protein and RNA N/A

into immature HIV at CD4 cell
membrane

7 Budding of immature HIV virus from ● Protease inhibitors

host cell to form mature HIV virus.
(Protease help to breaks long protein
chain in immature virus)
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.

Source: Scott, G. K., Saki, S. & Dong, S. A. (2011). Stem cell-based anti-HIV gene therapy,
Virology, 411(2), 260-272. https://doi.org/10.1016/j.virol.2010.12.039

Schematic illustrating HSC-based gene therapy approaches to treat HIV infection. The anti-HIV
factor (such as a siRNA to CCR5 or a molecularly cloned anti-HIV TCR) is cloned and
characterized (1) and made into a lentiviral vector (or other form enabling genetic transduction
of target cells) (2). HSCs are mobilized from the bone marrow of HIV infected individuals and
peripheral blood mobilized CD34+ cells are obtained by apheresis and cell sorting (3). CD34+
cells enriched with HSCs are then genetically transduced with the anti-HIV factor (4), and the
cells are then reinfused back into the individual (5). Following infusion, the anti-HIV gene
containing HSCs should migrate to the bone marrow where they take up residence as long-term
hematopoietic progenitors. Anti-HIV genes containing cells protected from infection should
undergo selection by HIV in the body and/or cells engineered to target HIV should respond to
the virus and proliferate (6). The effects of this are protection of anti-HIV gene-containing cells
(7a) or directed targeting of HIV or HIV infected cells by anti-HIV gene expressing cells (7b),
resulting in the regeneration of antiviral immune responses and targeted eradication of HIV.
Source: Ognenovska, K., Klemm, V., Ledger, S., Turville, S., Symonds, G., D. Kelleher, A., & L.
Ahlenstiel, C. (2019). Mechanisms for Controlling HIV-1 Infection: A Gene Therapy Approach.
IntechOpen. http://10.5772/intechopen.79669

Gene therapy delivery strategies; ex vivo lentivirus transduction of isolated patient

haematopoietic stem cells (HSC) and/or CD4+ T cells to deliver the gene modification versus
systemic, in vivo delivery of the gene therapy directly to the patient, which requires a cell
specific moiety to ensure targeted cell delivery.