Basics Of Chemotherapy, Anti-malarials & HIV Treatment Part 3

Question 1

Describe the mechanism of HIV

Answer 1

1. HIV binds to CD4 receptors on lymphocytes by gp120
2. Binding is aided by co-receptors CCR5 / CXCR4 on the lymphocyte
3. Fusion of HIV particle to cell surface allows the release of positive-strand HIV RNA, reverse transcriptase and integrase enzymes
4. Viral DNA is formed from RNA by reverse transcription (catalysed by reverse transcriptase)
5. This viral DNA is transported across the nucleus and integrates into the host DNA via integrase enzyme
6. New viral RNA is formed and used as genomic RNA to make viral proteins
7. Congregation of viral RNA and proteins at the cell surface forms a new, immature HIV particle
8. HIV virus is released, viral protease cleaves new polypeptides to create mature infectious virus

Question 2

Describe 3 qualities of HIV

Answer 2

1. Retrovirus
2. Positive-strand RNA
3. 15 genes

Question 3

What is a retrovirus?

Answer 3

An RNA virus which inserts a DNA copy of its genome into the host cell in order to replicate

Question 4

What is the difference between a nucleoSide and a nucleoTide?

Answer 4

NucleoSide = base + sugar
NucleoTide = base + sugar + phosphate

Question 5

What do reverse transcriptase (RT) inhibitors do?

Answer 5

Prevent HIV RNA being converted to HIV DNA via RT

Question 6

What do reverse transcriptase (RT) inhibitors do?

Answer 6

Prevent HIV RNA being converted to HIV DNA via RT

Question 7

Why is RT a target for chemotherapy?

Answer 7

RT is encoded for by the viral genome, is not present in humans

Therefore is a qualitative difference between the host and virally infected cells (targeting it will not have an effect on host cells)

Question 8

What are the 2 types of RT inhibitors?

Answer 8

1. Nucleoside RT inhibitors (NRTIs)
2. Non-nucleoside RT inhibitors (NNRTIs)

Question 9

What are the 4 nucleoside reverse transcriptase inhibitors (NRTIs) ?

Answer 9

AZT
DdC
Ddl
3TC

Question 10

What are nucleoside RT inhibitors (NRTIs)?

Answer 10

Analogs of naturally occurring nucleosides
Modified with the removal of the -OH molecule on the ribose molecule

Question 11

How do NRTIs (nucleoside RT inhibitors) inhibit RT?

Answer 11

1. NRTI converted to triphosphate nucleotide form by host kinases
2. Acts as a substrate for RT
3. Leads to the termination of the elongation of the DNA chain due to the removal of the hydroxyl (-OH) group from the ribose molecule

*the host DNA polymerase has a lower affinity for the modified nucleotide than RT so there is less effect on non-infected cells