L20 Anti-HIV drugs Flashcards
list important proteins involved in
HIV-host cell interaction
- gp120
- gp41:
- CD4: A primary receptor on the host cell (typically T-cells) that binds to gp120.
- CCR5: A coreceptor on the host cell used during the initial stages of infection.
Origin of HIV
HIV (Human Immunodeficiency Virus) originated from Simian Immunodeficiency Virus (SIV) found in primates. The virus likely crossed over to humans through the preparation and consumption of bushmeat.
Structure of HIV
HIV is a retrovirus with a roughly 9 kb RNA genome. Its structure includes:
Pol polyprotein: Contains protease, reverse transcriptase, and integrase enzymes.
Env polyprotein: Processes into gp120 and gp41, which are critical for viral entry into host cells.
(don’t need to know)
Gag polyprotein: Processes into matrix (MA), capsid (CA), nucleocapsid (NC), and P6
Accessory and regulatory proteins: These include six additional genes that assist in various stages of the viral life cycle and immune evasion .
Life cycle of HIV 1/2.binding and fusion
- Binding and Entry:
HIV binds to CD4 receptor on the surface of host cells (mainly T-cells) using gp120 protein. Binding induces a conformational change, allowing gp120 to interact with a coreceptor (CCR5 or CXCR4). Interaction exposes the gp41 protein, which facilitates the fusion of the viral and host cell membranes, allowing the viral RNA to enter the host cell.
Life cycle of HIV steps to know
- Binding
- Fusion
- Reverse Transcriptase
- Integration
- Maturation
Life cycle of HIV 3. Reverse transcription
Once inside, the viral RNA is reverse transcribed into double-stranded DNA by the viral reverse transcriptase enzyme.
Life cycle of HIV 4. Integration
The newly synthesized viral DNA is transported into the host cell nucleus and integrated into the host genome by the viral integrase enzyme.
Life cycle of HIV 5. maturation
After budding, the viral protease enzyme cleaves the Gag and Gag-Pol polyproteins into their functional forms, resulting in mature, infectious virions .
CD4/ CCR5/ CCR4
Helper T cells
C-C chemokine receptor 5;
initial infection
CXCR4 (C-X-C chemokine receptor
4; advanced disease)
gp120 and CD4 interaction
gp120-CD4 interaction → expose bind site for coreceptor (CCR5 or CXCR4)
Coreceptor binding → further conformational changes → expose gp41 and form channel for injection of HIV genetic material into the cell.
Then fusion process.
their interaction leads to a conformational change that will expose the binding sites for coreceptors (CCR5 or CXCR4). The coreceptor binding will lead to further conformational changes to expose gp41.
slow T cell depletion leads to ‘immune deficiency’ where they are
unable to fight against otherwise rare infections (opportunistic infections)
In a HIV host cell interaction there is also 2 factors
- persistent viral replication
- impair tumour immunosurveillance
CD4+T
Susceptible to HIV infection when there is a decline in CD4 leaving ppl more immunocompromised
Location on viral
gp120 and gp41
Found of surface of HIV particle and will interact with the host cell
HIV reverse transciptase is what type of dimer
heterdimer
