HIV Flashcards
What does HIV primarily infect?
CD4+ T cells
HIV gp120 protein binds to what?
CD4 receptors
What are the main HIV co-receptors?
CCR5
CXCR4
What are the key stages of HIV replication?
- gp120 binds CD4 receptor
- Fusion of viral and host membrane
- Uncoating of viral particle and release of viral material
- Reverse transcrip of viral RNA into DNA
- Import DNA into nucleus
- Integration of viral DNA into host DNA
- Transcrip of viral DNA to create new viral RNA
- Export of new viral RNA
- Translocation of viral RNA to create new viral protein
- Assembly of new viral RNA and protein at cell surface
- Budding of new viral particles
- Release of new viral particles
- Maturation of viral proteins
What opportunistic infections are people with HIV susceptible to?
Candidiasis Cytomegalovirus Herpes simplex virus TB Mycobacterium avium complex
What have most HIV drugs been developed against?
Reverse transcriptase
Protease
What are the 6 targets for HIV drugs?
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Protease inhibitors
Fusion inhibitors
Integrase inhibitors
CCR5 antagonists
What class drug is AZT?
NRTI
How do NRTIs work?
Act as chain terminators at the substrate binding site of reverse transcriptase
How do NNRTIs work?
Inhibit DNA repliation by binding at the allosteric non-bonding site of reverse transcriptase, causing a conformational change of the active site
What are protease needed for?
In reproduction cycle, they are needed to process GAG and POL polyproteins into mature HIV components
All approved protease inhibitors contain what bond instead of normal peptide bond?
Hydroxyethylene
What class of drug is fuzeon?
Fusion inhibitor
How does fusion work?
Blocks entry of HIV into cells. It mimics components of gp41 and displaces them, preventing normal fusion
What is the mechanism of HIV fusion?
- HIV approaches CD4+ T cell.
- gp120 binds to CD4.
- Conformational change, exposes gp41
- gp41 composed of HR1 and HR2
- Hydrophobic terminus of gp41 embeds into cell membrane.
- HR2 begins to coil into grooves of HR1
- Zipping destabolises both cell membranes and punches a hole
- HIV capsid pass through and infection occurs
What foes fuzeon mimic?
HR2 on gp41
What does fuzeon bind to?
HR1
What drug class in Maraviroc?
Entry inhibitor
How does Maraviroc work?
Blocks the attachment of HIV gp120 t CCR5 receptor
How do integrase inhibitors work?
Block integrase A and prevent the virus from adding its DNA into the DNA in CD4 cells.
What does HAART stand for?
Highly active anti-retroviral therpy
What does HAART do?
Generally takes 3 different antiretroviral drugs from at least 2 different classes
What does HAART prevent
resistance
What does HAART regimen comprise?
2 NRTIs
1 NNRTI, PI or II
What are the new challenges to HAART?
Intolerance and long term toxicity.
Lack of adherence.
Co-morbidities.
Increasing drug resistance.
What are fixed dose combinations?
Combinations of previous classes of HIV drugs in one pill
