Oncogenic viruses Flashcards
Viruses
- Causative
- Therapeutic
= viruses that transform normal cells
= vectors delivering anti-cancer cargo
Rous’ experiment sarcoma-induing agent in chickens
- Chicken with sarcoma in breast cancer
- Remove sarcoma + break up
- > cells lyse - Grind up sarcoma with sand
- Pass through fine-pore filter and collect filtrate
- Inject filtrate into young chicken
- Observe sarcoma in injected chicken
Fibiger
- hypothesis
- reasons for failure
Cancer is infectious
Found a parasite in a rat that caused cancer
Rat living conditions were dire
Rats only ate sugar
Cells weren’t proliferative - merely larger
- result of nutrient deficiency
RSV
- name
- infected cells
= Rous Sarcoma Virus
Change in behaviour of some cells
- normally have contact inhibition
BUT now form clumps
Viral DNA integration into host genome in:
RNA
DNA
RNA tumour viruses = intrinsic
DNA tumour viruses = rare and random event
Viral replication
- Virus attaches to plasma membrane
- Virus internalised + sheds capsid
- Uses host machinery to replicate and transcribe viral genome
- Components assemble
- Releases components
- Lethal to cell
Viral replication
- altered toxicity to host cell
Some viruses allow cell the option to continue dividing
-> produces more and more viral proteins
RNA virus replication
- process
- Enters cell + sheds envelope
- Reverse transcriptase makes DNA/RNA and then DNA/DNA double helix
- DNA copy integrated into host chromosome
- New virus particles assembled into protein coats
RNA virus replication
- what do all the new virus particles contain?
Reverse transcriptase
+ Capsid protein
+ Envelope protein
DNA virus replication
- process
- Virus enters cell and sheds coat
- DNA replicated and transcribed + translated
- Progeny virus particles assembled
- Exit cell
DNA virus replication
- what do all the new virus particles contain?
DNA
+ Coat protein
Provirus
- what is it?
= virus genome integrated into DNA of a host cell
Tumourigenicity
- what is it?
= ability of cultured cells to give rise to benign or malignant progressively growing tumours
Tumourigenicity
- how does it occur?
Viral genomes contain several human gene homologues
(cellular proto-oncogenes)
Infective viruses ‘kidnap’ porto-oncogenes
-> then transformed into oncogenes
Tumourigenicity
- process
1. ALV virion infection + reverse transcription = dsDNA provirus 2. dsDNA provirus integrates with host cell chromosomal DNA 3. If integrates upstream of c-src -> converts proto-oncogene into oncogene -> transcribed 4. packaged into capsid = RSV virion
When will ALV provirus lead to uncontrolled cell proliferation?
Only if ALV inserts into or before a gene responsible for cell division
e. g. upstream of c-myc
- > transcribed into myc mRNAs
HPV
- name
- what is it?
Human Papilloma Virus
Non-enveloped viruses composed of ds, genetically stable, closed circular DNA genome
HPV
- 4 types
- common in?
HPV-16 and 18
- common in ~70% of cervical carcinomas
HPV-6 and 11
- common in genital warts
HPV
- infection to cervical carcinoma
1,000,000 HPV-infected females
100,000 cervical dyslexia
8000 carcinoma in situ
1600 females with invasive cervical cancer
HPV
- % of cervical carcinomas that contain HPV DNA
- 4 types found in ~80% of HPV+ cancers
~90%
HPV-16, 18, 31 + 45
HPV
- how is its life cycle stealthy?
> occurs within epithelium
no viraemia (presence of virus in blood)
no cell death
no inflammation
can lead to immune deviation + virus persistence
HPV 16
- produces 8 proteins
L1 + L2
E5, E6 + E7
E1, E2, E4 + LCR
HPV 16
- L1 function
- L2 function
L1 = major capsid protein in virus particle
By itself, can assembled into capsomers and then from virus-like particles (VLPs)
L2 = minor capsid protein in virus particle
Binds to DNA
HPV 16
- E5 function
- E6 function
- E7 function
Cause proliferation
E5 = interaction with Epidermal Growth Factor (EGF)/ Platelet-Derived Growth Factor (PDGF)
E6 = Deregulation of p53 tumour suppressor protein
E7 = inactivation of Retinoblastoma (Rb) tumour suppressor protein
