DNA tumour viruses Flashcards
how many genotypes of HPV are there
> 100
what is the result of cutaneous genotypes of HPV
benign skin warts
what are the low risk genital genotypes of HPV
HPV-6 and 11 which cause warts
what are the high risk genital genotypes
hpv16 and 18
what can high risk hpv genotypes cause
intraepithelial lesions and no-genital cancers
describe the HPV genome
7-8kb double stranded circular genome
what are the barriers faced when trying to research HPV
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
how have researchers circumvented the issue of hpv species-specificness
transgenic mice
describe the structure of HPV
icosahedral capsized with non enveloped protein shell made up of mostly L1 and L2. DNA is complexed to histones
what is the URR region of the HPV genome
initiation of replication
what is the role of the E1 gene
viral replication
what is the role of the E2 gene in HPV genome
viral replication and transcription, specifically it is a critical transcriptional regulator
what is the role of the E4 gene in HPV
destabalisation of cytokeratin network
what is the role of the E5 hpv gene
mediation of mitogenic signals of growth factors as well as a role in protecting the virus from the immune system
what is the role of the E6 gene in HPV
cellular transformation which is key for progression to malignancy
what is the role of the E7 gene in HPV
cellular transformation and is key for progression to malignancy
what is the result of loss of E1 and E2 expression upon integration of HPV into the host genome
up regulation of E6 and E7 as E2 negatively regulates transcription
which proteins produced by hpv are considered to be viral oncoproteins
E5, 6 and 7
describe the structure and action of E6 protein
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
describe the structure and action of E7 protein
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
how does E6 promote p53 degradation
bind p53 along with a cellular ub ligase called E6-ap. this leads to displacement of E6, ubiquitination of p53 and then degradation
how does E7 cause eI2F dissociation from RB
it binds eI2F and dp-1
how does high risk hpv evade the immune system
it down regulates MHC1 at the level of transcription
what are some novel dan viruses associated with human cancers
human polyomavirus
what sort of virus is merkel cell carcinoma caused by
merkel cell polyomavirus
what sort of cancer is merkel cell carcinoma
skin cancer
describe the potential mechanism for how merkel cell polyomavirus transforms skin cells
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
