Lecture 12 - HPV Flashcards

1
Q

What is the genome of HPV?

A

dsRNA

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2
Q

Is HPV species specific?

A

Yes

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3
Q

How many groups of HPV are there in man?

What are these groups?

A
4
Cutaneous
Genital warts
Genital cancers
EV associated (hereditary)
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4
Q

What is HPV popularly known as?

A

Genital warts

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5
Q

What is the structure of the capsid of HPV?

A

Icosahedral symmetry

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6
Q

What are the segments of the HPV genome?

A

E 1-8

L 1-2

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7
Q

What are E and L genes?

A

E: early
L: late

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8
Q

How is HPV spread?

A

Skin - skin contact

HPV is present on the surface of skin and warts

There must be a scratch on the skin / mucous membrane

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9
Q

Describe the pathogenesis of HPV

A
  1. Virus enters at basal level (cut / scratch)
  2. E proteins produced, genome is episome
  3. Cell replication
  4. Episome copied –> multiple copies in each cell
  5. Late proteins made
  6. Self-assembly
  7. Virus filled keratinocytes shed from the curface
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10
Q

What enhances cell replication of HPV

A

E6

E7

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11
Q

At which point is the viral genome integrated into the cell?

A

It is never integrated, it ‘attaches’ to the host genome so that it replicates with the host cell

Daughter cells will have the episome

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12
Q

Where do HPV infections originate?

A

Basal layer

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13
Q

How does HPV get out of the host cells?

A

The don’t

They don’t lyse the cell, but are simply shed off in the keratinocytes

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14
Q

What is the structure of the episome?

A

Single covalently closed circular molecule of DNA

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15
Q

Why are warts seen in this infection?

A

Under E6 and E7 we get a lot of cell division, leading to the presence of benign warts

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16
Q

What are L1 and L2 responsible for?

When are they produced?

A

Capsid

They are produced in keratinocytes

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17
Q

How does HPV travel in the blood?

A

It doesn’t

The virus is only present in the skin

18
Q

What are the reasons for poor immune response induction in HPV infection?

A
  • no virus in blood
  • no lysis of cells –> no inflammation
  • no antigen taken to lymph nodes
19
Q

Is there ANY immune response to HPV?

A

Yes, but it is very weak

Against L1 and L2

20
Q

What sort of vaccines are needed for HPV?

A

Theraputic for warts

Theraputic for cervical cancer

Prophylactic to prevent infection

21
Q

What are some of the ‘old’ therapies for warts?

A
  • burning them off
  • poison
  • freeze
  • cut them off
22
Q

How may warts be treated with immunotherapy?

A
  • Interferon (anti-viral cytokine)

- Imiquod (TLR-7 agonist)

23
Q

What type of vaccine do we have for HPV?

A

VLPs: Virus like particles

24
Q

What makes up the HPV VLP vaccine?

A

Recombinant L1 protein

25
Q

What does the HPV VLP vaccine induce?

A
  • Virus neutralising antibody

- Cell-mediated response

26
Q

Is the HPV vaccine theraputic or prophylactic?

A

Prophylactic

27
Q

What do we see with DTH after immunisation?

A

Large cellular response

Many CD4+ and CD8+ cells

28
Q

What does ‘immunogenic’ mean?

A

It means that the substance (eg. antigen) will elicit an immune response

29
Q

How does the VLP vaccine work?

A

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

30
Q

Describe the antibody production when GARDASIL is administered compared to a natural infection

A

GARDASIL: many times more antibodies than natural infection

31
Q

How is GARASIL administered?

A

Intramuscularly

32
Q

Is GARDASIL effective against strains not in the vaccine?

A

No

33
Q

How effective is GARDASIL against genital wart strains?

A

9/10

34
Q

How many HPV genotypes are there?

A

Over 100

35
Q

Where do we need the immunity from the vaccine most?

Does the vaccine supply this?

A

The mucosa

We don’t know how long protection lasts here

36
Q

What about men?

A

Anal cancer can occur in men

The vaccine can be purchased by men

37
Q

How long would it take to eradicate HPV?

A

5-6 generations

38
Q

What can HPV infection also lead to?

A

HPV infection can lead to cervical dysplasia, sometimes leading to cervical cancer

39
Q

Describe how HPC infection can lead to cervical cancer

A
  1. HPV randomly integrated into the host genome
  2. Capsid proteins lost
  3. IF E2 is lost, we now have no down regulation of E6 and E7
  4. E6 and E7 interact with p53 and pRB
  5. Continual cell cycling, no apoptosis
40
Q

Why is it hard to make a vaccine for cervical cancer?

A
  • Keratinocytes resistant to killing by CTL

- Cancerous cells rarely have MHC I

41
Q

What vaccines do we have for cervical cancer?

What are they made up of?

A

Theraputic

Based on E7