HPV & HIV viral pathogens

Question 1

Why are DNA detection methods used for HPV?

Answer 1

Bc can’t be grown in cell culture

Question 2

Name two high risk HPV types and two low risk HPV types?

Answer 2

Hi risk: 16, 18 (common)
Lo risk: 6, 11 = genital warts

Question 3

What human cellular proteins do the HPV E6 proteins interact and what is the effect?

Answer 3

• E6 binds to other cell components (BRAC1, ras oncogene) = no apoptosis
• E6-AP (assoc. protein) “complex” => binds to binding site/s & aggregates p53 tumour suppressor protein
• Core: mediates degradation after E6 binding
• C terminus: not mediate (*low risk HPV)
• Hi risk HPV: binds to both sites

Question 4

How are HPV genotypes defined?

Answer 4

• Cutaneous (=skin warts): Low risk (6, 11)
• mucosal (oncogenic): High risk (16, 18)

Question 5

What are the steps required for progression to cervical cancer from HPV?

Answer 5

1. Inoculation of HPV: Males are reservoir for HPV
2. HPV infection of cells: microwounds allows HPV to get to basal cells expressing a-6-integrin = entry in cell
3. Integration: HPV DNA integrates w/ human DNA => break point at E2 (, E5* & late genes) => E6 & E7 expressed => E6 binds p53 & E7 binds to pRb = cell cycle not stopped (@G1) & no apoptosis => progeny viruses released when Epi. cell shed
   *E5 transport MHC class 1

Question 6

How is the vaccine for HPV made?

Answer 6

Vaccine against Virus Like Particles (VLP)
- L1 region of HPV => L1 Protein => self-assemble into VLP
- VLP: are capsid w/ not DNA inside = not cause HPV disease (acting like decoys for I.Sys)

Question 7

Describe the life cycle of Retroviruses (Class 6) e.g. HIV**

Answer 7

ss(+)RNA w/ dsDNA intermediate
1. Virus binds to CD4 on T lymph -> entry (lose membrane)
2. lose capsid
3. mRNA(/+) -> DNA by RVS transcriptase/RNA dependent DNA pol
4. dsDNA integrates in host genome
5. translation -> assembly
6. viral budding

Question 8

What are the three main genes of Retroviruses and what do they code for?

Answer 8

• Groups Specific Antigen (gag): cores & structural proteins (matrix p17 & Capside p24 protein)
• Polymerase (pol): RVS transcriptase (RNA->DNA), pol, RNAase p66, protesase p9, integrase p32 (integrate in genome)
• Envelope (env): retrovira; coat protein gp120 (attaches CD4), gp41 (fuse env to mem)

Question 9

Why does HIV mutations occur so rapidly?

Answer 9

bc RVS transcriptase lacks 3’ to 5’ proof-reading of DNA transcript = error prone = Hi rate of mutation of HIV virus

Question 10

What are endogenous and exogenous Retroviruses?

Answer 10

Endo: integrate in host genome & passed onto following generations
Exo: integrate in host genome but not get passed to following generations

Question 11

What is the main receptor for HIV and what are the co-receptors

Answer 11

Main: CD4 on T lymph, macroph, langerhan
Co-receptor:
- CCR5 on macroph (M tropic): enters macrophage @ early infect.
- CXCR4 on T helper lymph (T cell tropic): late in infection

Question 12

What are the two main factors inhibiting vaccine design for HIV?

Answer 12

• due to rapid mutations of virus
• Glycan shield: highly glycosylated gp120 = shield epitope from Aby binding (still allowing receptor binding)

Question 13

How was the Berlin patient cured of HIV?

Answer 13

• male infected w/ HIV & Dx w/ AML
• Stem-cell transplant w/ CD34+ PB stem cells
• replaced old stem cells = removed latent virus

Question 14

What human cellular proteins do the HPV E7 proteins interact and what is the effect?

Answer 14

• binds to retinoblastoma tumour suppressor protein (pRb)
  > mimic phosphorylation of pRb => release E2F => activates genes = progrssion of cell cycle to S phase
  *Hi risk: bind to pRb w/ 10 fold affinity than low risk HPV