DNA tumour viruses

Question 1

how many genotypes of HPV are there

Answer 1

> 100

Question 2

what is the result of cutaneous genotypes of HPV

Answer 2

benign skin warts

Question 3

what are the low risk genital genotypes of HPV

Answer 3

HPV-6 and 11 which cause warts

Question 4

what are the high risk genital genotypes

Answer 4

hpv16 and 18

Question 5

what can high risk hpv genotypes cause

Answer 5

intraepithelial lesions and no-genital cancers

Question 6

describe the HPV genome

Answer 6

7-8kb double stranded circular genome

Question 7

what are the barriers faced when trying to research HPV

Answer 7

it is difficult to grow in cultured cells and is species-specific so human hpv will only grow in human cells and mouse hpv will only grow in mouse cells

Question 8

how have researchers circumvented the issue of hpv species-specificness

Answer 8

transgenic mice

Question 9

describe the structure of HPV

Answer 9

icosahedral capsized with non enveloped protein shell made up of mostly L1 and L2. DNA is complexed to histones

Question 10

what is the URR region of the HPV genome

Answer 10

initiation of replication

Question 11

what is the role of the E1 gene

Answer 11

viral replication

Question 12

what is the role of the E2 gene in HPV genome

Answer 12

viral replication and transcription, specifically it is a critical transcriptional regulator

Question 13

what is the role of the E4 gene in HPV

Answer 13

destabalisation of cytokeratin network

Question 14

what is the role of the E5 hpv gene

Answer 14

mediation of mitogenic signals of growth factors as well as a role in protecting the virus from the immune system

Question 15

what is the role of the E6 gene in HPV

Answer 15

cellular transformation which is key for progression to malignancy

Question 16

what is the role of the E7 gene in HPV

Answer 16

cellular transformation and is key for progression to malignancy

Question 17

what is the result of loss of E1 and E2 expression upon integration of HPV into the host genome

Answer 17

up regulation of E6 and E7 as E2 negatively regulates transcription

Question 18

which proteins produced by hpv are considered to be viral oncoproteins

Answer 18

E5, 6 and 7

Question 19

describe the structure and action of E6 protein

Answer 19

around 150aa and contain 2 zinc fingers they’re transcriptional activators and high-risk E6 binds to p53 and directs its degradation as well as other proteins including those involved in DNA repair, pro-apoptotic factors, transcription factors and growth suppressors

Question 20

describe the structure and action of E7 protein

Answer 20

around 100aa also transcriptional activators. E7 binds RB and activates eI2F transcription factor which surpasses apoptosis allowing the virus to complete replication to guarantee its own survival

Question 21

how does E6 promote p53 degradation

Answer 21

bind p53 along with a cellular ub ligase called E6-ap. this leads to displacement of E6, ubiquitination of p53 and then degradation

Question 22

how does E7 cause eI2F dissociation from RB

Answer 22

it binds eI2F and dp-1

Question 23

how does high risk hpv evade the immune system

Answer 23

it down regulates MHC1 at the level of transcription

Question 24

what are some novel dan viruses associated with human cancers

Answer 24

human polyomavirus

Question 25

what sort of virus is merkel cell carcinoma caused by

Answer 25

merkel cell polyomavirus

Question 26

what sort of cancer is merkel cell carcinoma

Answer 26

skin cancer

Question 27

describe the potential mechanism for how merkel cell polyomavirus transforms skin cells

Answer 27

in immunosupressed or elderly patients the virus enters merkel cells, integrates with the genome then undergoes a second maturation event which truncates the t antigen gene so that it is not able to replicate but is able to drive cell survival