Lec 10 - Retroviruses and Hepadnavirus replication

Question 1

What are the 2 types of retroviridae and what human cell do they target?

Answer 1

1. Endogenous: ancient germline infection in 4-8% of population
2. Exogenous: horizontally transferred infection
   Infect somatic cells

Question 2

List the key components of HIV-1

Answer 2

• Diploid ssRNA with nucleocapsid
• tRNA lys primer
• RT/RdRp, integrase, protease
• gp120/SU and gp41/TM with fusion domain
• gag, pol and env genes

Question 3

Why is HIV-1 so diverse?

Answer 3

High mutation rate from RT’s low fidelity from lack of proofreading

Question 4

Describe the 8 steps of HIV-1’s replication cycle

Answer 4

1. gp120 binds CD4. gp120 V3 binds CXCR5 or CCR4 coreceptor
2. Fusion by gp41
3. Reverse transcription inside capsid
4. Nuclear import and uncoating
5. Integration of cDNA by integrase
6. Transcription during antigenic stimulation
7. Export RNA from nucleus for assembly
8. Maturation by protease

Question 5

What are the 2 domains of RT?

Answer 5

1. P66 for polymerase activity
2. p51 for RNase H activity

Question 6

Describe how HIV-1 replicates its genome

Answer 6

1. tRNA binds to primer binding site (PBS)
2. (-) cDNA synthesised in 5’ direction with RNase H degrading template
3. (-) cDNA jumps and binds R with its R’ for extension
4. RNase H degrades template so only (-) cDNA
5. PPT’ primer for (+) cDNA
6. RNase H degrades template so only cDNA
7. (+) cDNA jumps to PBS’ on (-) cDNA
8. Provirus with LTRs both ends

Question 7

What do HIV-1’s LTRs do and how?

Answer 7

Control transcription by transcription binding sites and promoters U3, U5 and R

Question 8

What is the function of HIV-1’s accessory protein TAT?

Answer 8

Promotes elongation. Bound by Tar then binds kinase to phosphorylate polymerase

Question 9

What are HIV-1’s polyproteins and which contains the key enzymes?

Answer 9

gag-pol with enzymes, gag and env

Question 10

Describe HBV’s genome

Answer 10

Circular gapped dsDNA genome with short RNA section on short strand and P protein on long strand. Triplex region where circle overlaps.

Question 11

How does HBV evade immunity?

Answer 11

Filamentous form without genome to redirect immunity

Question 12

Describe HBV’s replication in the nucleus and why it remains latent

Answer 12

1. Repair gap to cccDNA
2. Transcribe pgRNA
3. Reverse transcribe pgRNA to cDNA provirus
   No integrase means latent in nucleus