Oncogenic Viruses Flashcards
Which 4 gene types are damaged during oncogenesis?
Proto-oncogenes, tumour suppressor genes, regulating apoptosis, DNA repair
What are the oncogenic RNA viruses?
Oncoretroviruses
What are the oncogenic DNA viruses?
Papillomaviruses, herpesviruses
Which types of viruses cause leukaemias and lymphomas?
The alpha, beta, gamma, delta and epsilon viruses
What type of virus is HIV?
Lentivirus
Which species are affected by the alpha, beta, gamma, delta and epsilon viruses?
All veterinary
Why do retroviruses need close or blood contact?
Enveloped and unstable
What is the genome like in retroviruses?
ss +ve sense RNA with terminal repeat elements
Which type of virus has gag pol and env?
Retrovirus
What does gag do?
Structural
What does pol do?
Repliation enzymes
What does env do?
The envelopes
What happens to the DNA provirus in retroviruses?
Integrates into the host genome
What do the LTR of a retrovirus contain?
Enhancer elements
What can some acutely oncogenic viruses replace env with?
A host oncogene
What happens if you replace env with a host oncogene?
Replication defective
How can you become acutely oncogenic whilst remaining replication competent?
Just add and oncogene
What is the genome like in replication competent but weakly oncogenic viruses?
They have gag, pol and env with accessory ORFs which act as oncoproteins
Why can oncogenic retroviruses only affect replicating cells e.g. lymphoid, haematopoietic?
Can’t enter the nuclear membrane so the pre-integration complex must wait until cell division
How are exogenous viruses transmitted?
Horizontal
How are endogenous viruses transmitted?
Provirus in germline so vertical transmission
How do some viruses encode v-onc?
Pick up a proto-oncogene and lose env/pol (take a highly active oncogene into the host cell)
Which mutations can v-onc contain affecting proteins?
Alter normal protein function or regulation e.g. increase stability or cause constitutive activation
What happens if v-onc fuses to gag?
Transports the oncoprotein to the cell membrane where it functions as a signal transporter.
What is expression of v-onc like?
Not controlled as viral LTRs are strong and not affected by cellular regulation.
What is replication like in viruses encoding v-onc?
Usually defective but can be competent.
How do you get cis-activation of a cellular oncogene?
Provirus inserts close to c-onc and LTR acts as a promoter or enhancer
What is replication and oncogenesis like in cis-activation of a cellular oncogene?
Weakly oncogenic and won’t transform in vitro, but competent for replication
Why are tumours clonal in cis-activation of a cellular oncogene?
The cells all have one preferred integration site
What is replication and oncogenesis like in trans-activation by an essential virus protein?
Weakly oncogenic, long incubation, replication competent
Are the tumours clonal in in trans-activation by an essential virus protein?
Yes, but there is no preferred integration site
What clinical signs are papillomaviridae assocaited with?
Warts
Can you culture papillomavirus?
No
Where are papillomavirus trophic for?
Squamous epithelium, as depend on terminal squamous epithelial cell differentiation to replicate.
Are papillomavirus benign or malignant?
Benign usually
What is the structure of papillomaviruses?
No envelope so stable
What is genome of papillomaviruses like?
ds circular DNA, with early replication and late parts
Which are the oncogenic gene products in papillomaviruses?
Early e.g. E5,6,7
Which cell must be exposed for a papillomavirus to enter?
Basal stem cell
What does early gene expression in papillomavirus push replication of?
Basal stem cells
How does late gene expression begin in papillomaviruses?
Switch of cells into mature keratinocytes switches replication from plasmid to vegetational replication and late gene expression begins
How does E6 interfere with cell cycle control?
Interacts with p53 and causes its degradation
How does E7 interfere with cell cycle control?
Interacts with pRB and causes E2F-1 to always be released so the cell cycle continues
What is the cofactor in CRPV skin carcinoma?
Methylcholanthrene
Which type of herpesviruses are the oncogenic ones?
Gamma
How do herpesviruses often become oncogenic?
Species jump
What are two methods of activation of cellular oncogenes?
Cis or trans
