Oncogenic viruses Flashcards

1
Q

Viruses

  • Causative
  • Therapeutic
A

= viruses that transform normal cells

= vectors delivering anti-cancer cargo

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2
Q

Rous’ experiment sarcoma-induing agent in chickens

A
  1. Chicken with sarcoma in breast cancer
  2. Remove sarcoma + break up
    - > cells lyse
  3. Grind up sarcoma with sand
  4. Pass through fine-pore filter and collect filtrate
  5. Inject filtrate into young chicken
  6. Observe sarcoma in injected chicken
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3
Q

Fibiger

  • hypothesis
  • reasons for failure
A

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

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4
Q

RSV

  • name
  • infected cells
A

= Rous Sarcoma Virus

Change in behaviour of some cells
- normally have contact inhibition
BUT now form clumps

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5
Q

Viral DNA integration into host genome in:
RNA
DNA

A

RNA tumour viruses = intrinsic

DNA tumour viruses = rare and random event

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6
Q

Viral replication

A
  1. Virus attaches to plasma membrane
  2. Virus internalised + sheds capsid
  3. Uses host machinery to replicate and transcribe viral genome
  4. Components assemble
  5. Releases components
  6. Lethal to cell
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7
Q

Viral replication

- altered toxicity to host cell

A

Some viruses allow cell the option to continue dividing

-> produces more and more viral proteins

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8
Q

RNA virus replication

- process

A
  1. Enters cell + sheds envelope
  2. Reverse transcriptase makes DNA/RNA and then DNA/DNA double helix
  3. DNA copy integrated into host chromosome
  4. New virus particles assembled into protein coats
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9
Q

RNA virus replication

- what do all the new virus particles contain?

A

Reverse transcriptase
+ Capsid protein
+ Envelope protein

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10
Q

DNA virus replication

- process

A
  1. Virus enters cell and sheds coat
  2. DNA replicated and transcribed + translated
  3. Progeny virus particles assembled
  4. Exit cell
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11
Q

DNA virus replication

- what do all the new virus particles contain?

A

DNA

+ Coat protein

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12
Q

Provirus

- what is it?

A

= virus genome integrated into DNA of a host cell

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13
Q

Tumourigenicity

- what is it?

A

= ability of cultured cells to give rise to benign or malignant progressively growing tumours

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14
Q

Tumourigenicity

- how does it occur?

A

Viral genomes contain several human gene homologues
(cellular proto-oncogenes)

Infective viruses ‘kidnap’ porto-oncogenes
-> then transformed into oncogenes

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15
Q

Tumourigenicity

- process

A
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
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16
Q

When will ALV provirus lead to uncontrolled cell proliferation?

A

Only if ALV inserts into or before a gene responsible for cell division

e. g. upstream of c-myc
- > transcribed into myc mRNAs

17
Q

HPV

  • name
  • what is it?
A

Human Papilloma Virus

Non-enveloped viruses composed of ds, genetically stable, closed circular DNA genome

18
Q

HPV

  • 4 types
  • common in?
A

HPV-16 and 18
- common in ~70% of cervical carcinomas

HPV-6 and 11
- common in genital warts

19
Q

HPV

- infection to cervical carcinoma

A

1,000,000 HPV-infected females

100,000 cervical dyslexia

8000 carcinoma in situ

1600 females with invasive cervical cancer

20
Q

HPV

  • % of cervical carcinomas that contain HPV DNA
  • 4 types found in ~80% of HPV+ cancers
A

~90%

HPV-16, 18, 31 + 45

21
Q

HPV

- how is its life cycle stealthy?

A

> occurs within epithelium
no viraemia (presence of virus in blood)
no cell death
no inflammation
can lead to immune deviation + virus persistence

22
Q

HPV 16

- produces 8 proteins

A

L1 + L2

E5, E6 + E7

E1, E2, E4 + LCR

23
Q

HPV 16

  • L1 function
  • L2 function
A

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

24
Q

HPV 16

  • E5 function
  • E6 function
  • E7 function
A

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

25
Q

HPV 16

  • E1 function
  • E2 function
  • E4 function
  • LCR function
A

E1 = replication of viral DNA, maintenance of viral episome, essential for viral replication + control of gene transcription

E2 = essential for viral replication and repression of E6 + E7

E4 = forms filamentous cytoplasmic networks

LCR = origin of DNA replication + regulation of HPV gene expression

26
Q

HPV and cervical carcinoma

- process

A
  1. Infection in basal epithelial layers where viral genome is maintained as episome
  2. Viral replication occurs in supra-basal layers
27
Q

Cervical carcinoma progression

- CIN 1

A

= mild dysplasia , lower third of epithelium

  • full complement of HPV DNA and proteins produced
  • infectious virus produced in mature squamous cell layer
28
Q

Cervical carcinoma progression

- CIN 2

A

= Moderate dysplasia, lower 2-thirds of epithelium

  • more extensive production of E6 + E7 proteins
  • less extensive production of viral DNA and late proteins than CIN I
29
Q

Cervical carcinoma progression

- CIN 3

A

= Severe dysplasia, total involvement of epithelium

  • V high level of E6 + E7 production
  • Little production of late proteins or viral DNA
30
Q

HPV and cervical carcinoma

- order of HPV proteins produced

A

Virus infects basal cells
= E1 and E2

Virus and cell replication
= E1, E2, E5, E6 and E7

Viral DNA amplification in non-dividing cells
= L1, L2 and E4

Virus assembly
= viral gene expression

31
Q

HPV

- E7 enables cell proliferation

A

Activates pathway that enables ds break repair to happen faster

  • > genome is more stable
  • > cell can continue to proliferate
32
Q

HPV

- E6 and apoptosis

A

E6 interacts with p53

-> stabilises anti-apoptotic proteins

33
Q

E7 deregulates TSG protein RB

A
  1. E5 stabilises E7
  2. Rb interacts with E7
  3. Enables aberrant proliferation
  4. Apoptosis

OR Immobilisation

  • >
    1. Genomic instability
    2. Transformation
34
Q

E6 deregulates TSG protein p53

A
  1. E5 stabilises E6
  2. p53 interacts with E6
  3. Inhibits apoptosis

OR activates immortalisation

  • >
    1. Genomic instability
    2. Transformation