Virology: Papillomaviruses and Polyomaviruses - Permissive vs non permissive infection

Question 1

Explain Permissive infection.

Answer 1

• efficient viral replication
• viral genome is not integrated
• complete life cycle and progeny viruses are made
• aka this is the normal/ideal situation for the virus

Question 2

Explain non-permissive infection.

Answer 2

• no, or poor viral replication
  -viral genome is integrated
• life cycle is not completed … no progeny viruses are made.
  L> this integration that occurs increases the risk of cancer via proto-oncogene being amplified and turned into an oncogene.

Question 3

Why are papillomaviruses and polyomaviruses tumour viruses?

Answer 3

• early gene expression (E6 and E7 in HPV and LT in SV40)
• cause hyper-proliferation making the cells have a selective advantage over neighbouring cells.
• Early viral genes always present and continuous expression of these viral onco proteins can lead to cell transformation and tumour growth.

Question 4

Viral DNA integration, explain it. 
L> is it norm?
L> good for the virus? How about the host?
L> HPV?
L> MCPV?
L> Consequences?

Answer 4

-integration (remember) is not the NORM
-abrogates virion production - dead end for the virus
- HPV genome often integrated in cancers
- In MCPV often integrated in Merkel cell carcinomas
- Consequence: continuous expression of viral early proteins
L> deregulate host tumour suppressor proteins
L> increased genomic instability of host
L> increased risk of cells acquiring cancer causing mutations (rare event)

Question 5

How many different papillomaviruses can infect us?

Answer 5

• 200

- HOW-FREAKING-EVER only 12 have been found to be cancer linked.

Question 6

HPV causes what?

Answer 6

• warts – oh how cute

Question 7

HPV causes warts:

-infects what, causing what?

Answer 7

• epithelial cells - skin, linings of anogenital tract and oropharynx
• can cause hand and foot warts
• genital warts and laryngeal papillomas (benign disease)

Question 8

HPV is linked with what cancers?

Answer 8

• cancer of the uterine cervix
• cancer of the oropharynx
• non-melanoma skin cancers
• ONLY some HPV types are associated with cancers eg HPV16 and HPV18 are the high risk types.

Question 9

HPV and Cancer. Lets hear the stats. What are the cancers.

Answer 9

• Worldwide, 610,000 cancers associated with high risk HPV
• nearly all cervical cancers contain high risk HPV DNA
• High risk HPV associated with subset of head and neck cancers
• High risk HPV associated with non-melanoma skin cancers

Question 10

Controlling HPV infection and disease: 
- how common is it?
L> women?
-cervical cancer stats?
- how do they test for it?Prevention benefits?

Answer 10

• most common sexually transmitted infection via spread by surface to surface contact. 105 million women have an HPV16 or 18 infection. It is acquired very quickly and most of the time you would not know you have been infected.
• Cervical cancer is the third most common female cancer worldwide with nearly 500,000 new cases per year (274,000 deaths )
• cytological abnormalities in the cervix are monitored by the cervical smear aka pap test….starting at age 25. (large nucleus + condensed chromosomes)
• 4/5 of cervical cancer cases in UK prevented by the NHS screening programme

Question 11

Explain HPV L1 capsid protein wrt a vaccine for HPV.

Answer 11

• L1 is the major capsid protein
• HPV16L1 protein was found to be expressed in insect cells
• assembled into empty particles
• virus like particles (VLP)
• basis for the HPV vaccine
• *L1 expressed very similar to native particles…aka do not contain viral DNA and therefore no infection.

Question 12

What are the two HPV vaccines out there.

Answer 12

1. Cervarix: bivalent, HPV16 and HPV18 VLPs. HPV16 and 18 major HPV types in cervical cancers approx 70%
2. Gardasil:quadrivalent HPV16, 18 but also 6, 11 VLPs. HPV6 and 11 cause genital warts.

Question 13

How does the HPV vaccine work. How effective is it at blocking infection?

Answer 13

• block infection with HPV16 and HPV18 - neutralizing antibodies
• nearly 100% effective at prevention of HPV16 and 18 infection

Question 14

Vaccines:

- when should women be vaccinated ?

Answer 14

• before onset of sexual activity so around 12/13

Question 15

Vaccines:

- Can they cure HPV induced cancers?

Answer 15

• no

- they are prophylactic and not therapeutic vaccines aka it only blocks the infection

Question 16

What are the two types of infection that papillomaviruses and polyomaviruses can take?

Answer 16

• Permissive infection

- Non-permissive infection

Question 17

Do vaccinated women need to go for cervical smear screening?

Answer 17

• yes they do since the vaccine only protects them against the two high risk HPVs when there 12 KNOWN CANCER LINKED ONES….and 188 unknown

Question 18

Should boys be vaccinated??-

Answer 18

• not cost effective
• highly debated
• there is a slight increase in occurrence of boys getting head and neck cancers which is what people in favour of the vaccine being delivered to them argue

Question 19

Cervical cancer is most common where?

Answer 19

• in less developed areas of the world.
• 80% occur in less developed parts…
• UK the vaccine is being delivered in schools but in the US it is not happening and therefore there is a higher occurrence
  L> especially in states with low SES