Lecture 12 - HPV Flashcards
What is the genome of HPV?
dsRNA
Is HPV species specific?
Yes
How many groups of HPV are there in man?
What are these groups?
4 Cutaneous Genital warts Genital cancers EV associated (hereditary)
What is HPV popularly known as?
Genital warts
What is the structure of the capsid of HPV?
Icosahedral symmetry
What are the segments of the HPV genome?
E 1-8
L 1-2
What are E and L genes?
E: early
L: late
How is HPV spread?
Skin - skin contact
HPV is present on the surface of skin and warts
There must be a scratch on the skin / mucous membrane
Describe the pathogenesis of HPV
- Virus enters at basal level (cut / scratch)
- E proteins produced, genome is episome
- Cell replication
- Episome copied –> multiple copies in each cell
- Late proteins made
- Self-assembly
- Virus filled keratinocytes shed from the curface
What enhances cell replication of HPV
E6
E7
At which point is the viral genome integrated into the cell?
It is never integrated, it ‘attaches’ to the host genome so that it replicates with the host cell
Daughter cells will have the episome
Where do HPV infections originate?
Basal layer
How does HPV get out of the host cells?
The don’t
They don’t lyse the cell, but are simply shed off in the keratinocytes
What is the structure of the episome?
Single covalently closed circular molecule of DNA
Why are warts seen in this infection?
Under E6 and E7 we get a lot of cell division, leading to the presence of benign warts
What are L1 and L2 responsible for?
When are they produced?
Capsid
They are produced in keratinocytes
How does HPV travel in the blood?
It doesn’t
The virus is only present in the skin
What are the reasons for poor immune response induction in HPV infection?
- no virus in blood
- no lysis of cells –> no inflammation
- no antigen taken to lymph nodes
Is there ANY immune response to HPV?
Yes, but it is very weak
Against L1 and L2
What sort of vaccines are needed for HPV?
Theraputic for warts
Theraputic for cervical cancer
Prophylactic to prevent infection
What are some of the ‘old’ therapies for warts?
- burning them off
- poison
- freeze
- cut them off
How may warts be treated with immunotherapy?
- Interferon (anti-viral cytokine)
- Imiquod (TLR-7 agonist)
What type of vaccine do we have for HPV?
VLPs: Virus like particles
What makes up the HPV VLP vaccine?
Recombinant L1 protein
What does the HPV VLP vaccine induce?
- Virus neutralising antibody
- Cell-mediated response
Is the HPV vaccine theraputic or prophylactic?
Prophylactic
What do we see with DTH after immunisation?
Large cellular response
Many CD4+ and CD8+ cells
What does ‘immunogenic’ mean?
It means that the substance (eg. antigen) will elicit an immune response
How does the VLP vaccine work?
The vaccine contains only the capsid protein
Antibodies are made to the capsid
When exposed with the virus, the immune system is primed
Antibodies neutralise the HPV
Describe the antibody production when GARDASIL is administered compared to a natural infection
GARDASIL: many times more antibodies than natural infection
How is GARASIL administered?
Intramuscularly
Is GARDASIL effective against strains not in the vaccine?
No
How effective is GARDASIL against genital wart strains?
9/10
How many HPV genotypes are there?
Over 100
Where do we need the immunity from the vaccine most?
Does the vaccine supply this?
The mucosa
We don’t know how long protection lasts here
What about men?
Anal cancer can occur in men
The vaccine can be purchased by men
How long would it take to eradicate HPV?
5-6 generations
What can HPV infection also lead to?
HPV infection can lead to cervical dysplasia, sometimes leading to cervical cancer
Describe how HPC infection can lead to cervical cancer
- HPV randomly integrated into the host genome
- Capsid proteins lost
- IF E2 is lost, we now have no down regulation of E6 and E7
- E6 and E7 interact with p53 and pRB
- Continual cell cycling, no apoptosis
Why is it hard to make a vaccine for cervical cancer?
- Keratinocytes resistant to killing by CTL
- Cancerous cells rarely have MHC I
What vaccines do we have for cervical cancer?
What are they made up of?
Theraputic
Based on E7
