HPV

Question 1

Structure of HPV

Answer 1

• Small, non-enveloped dsDNA (circular genome > episome)
• only replicates in skin/epithelia
• doesnt culture well

Question 2

main groups of HPV

Answer 2

• Cutaneous warts (HPV 1, 2)
• Genital warts (HPV 6, 11)
  ○ Most common STI that people go to the doctor for
• Genital/other cancers (HPV 16, 18)
  EV (Epidermodysplasia verruciformis) (HPV 5, 8)

Question 3

Important proteins in HPV

Answer 3

Capsid proteins: L1 and 2
E2: links the viral episome to DNA in mitotic chromosome on the spindle ensuring partitioning of the episomes
- E6/7: enhances replication

Question 4

Replication of HPV

Answer 4

1. enters cells in the basal layer so that it can be replicated in daughter cells
2. early proteins are produced
3. cell replication enhanced by E6/7
4. multiple copies of episome made in each cell
5. late proteins and E4 made, viral genomes packaged into virions
6. virus filled keratinocytes are shed from surface

Question 5

Skin innate immunity

Answer 5

• Little or no antigen taken up by dendritic cells in the skin
• Suppression of antigen recognition and signalling by HPV proteins > Toll Like Receptor 9
• Not a lot of inflammatory response
  Little or no viral antigen to travel to lymph nodes

Question 6

Adaptive immune response HPV

Answer 6

Activated T cells will circulate lower layers of skin
- Weak reaction and comes late
- Antibody to capsid proteins (L2 and 1)
○ Protective (stops being reinfected) not therapeutic
○ Antibody recognises conformation-dependent epitopes
- Antibody to early proteins
○ Predominately E7, sometimes E2 (but its in chromosome so slow immune response)
Associated with invasive HPV16

Question 7

Regulatory signals in cells

Answer 7

• RB: stop transition from G1 to S stage
  ○ stops DNA synthesis by sequestering the E2F family of transcription factors, and so putting a break on the cell cycle
• P53 proofreads DNA is a transcription factor that induces expression of proteins that arrest the growth of the cell and initiate apoptosis

Question 8

E6 interaction with cell regulatory mechanisms

Answer 8

• overrides
• in malignant cells, HPV DNA is randomly integrated into the host genome, causing the loss of several genes
• if E2 is lost, then cancerous transformations are more likely to occur

Question 9

PAP stain

Answer 9

• can identifies HPV, not type and observe dysplasia

Question 10

Vaccines HPV

Answer 10

• Three types of vaccine
  ○ Therapeutic vaccine to treat warts
  ○ Prophylactic vaccine to prevent HPV
  Therapeutic vaccine to treat cervical cancer

Question 11

Papilloma virus-like particles

Answer 11

• Recombinant L1 (capsid) protein
  
  • Self assembles into capsid that looks like virions and binds to cells
  • More effective because it is intramuscular
  • Effective inducers of virus-neutralising antibody and can induce a cell-mediated response
    Can be used therapeutically

Question 12

GARDASIL vaccine

Answer 12

• VLP vaccine based on L1 protein
  
  • Vaccine is intramuscular
  • Elicits antibody titres many times higher than those seen following natural infection
  • No guaranteed efficacy against strains not in the vaccine

Question 13

cervical screening

Answer 13

does not say if the HPV DNA is from abnormal cells