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Medical Microbiology > 4 Viruses and Cancer > Flashcards

4 Viruses and Cancer Flashcards

1
Q

what does HBV and HCV cause

A

hepatocellular carcinoma

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2
Q

what does EBV cause

A

nasopharyngeal carcinoma
Burkitt’s lymphoma
Hodgkins disease

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3
Q

what does HPV cause

A

cervical carcinoma

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4
Q

what does HHV-8 cause

A

Kaposi’s sarcoma

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5
Q

what does HTLV-1 cause

A

adult T cell leukaemia/lymphoma

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6
Q

what does MCV cause

A

Merkel cell cancers

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7
Q

Criteria viruses and cancer

A
  • epidemiology
  • virus in tumour tissue
  • mechanisms of oncogenesis
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8
Q

Mechanisms of Oncogenesis

A
  • modulation of cell cycle control
  • modulation of apoptosis
  • ROS mediated damage
  • additional events
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9
Q

cell cycle S

A

synthesis

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10
Q

cell cycle G2

A

Gap 2

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11
Q

cell cycle M

A

mitosis

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12
Q

cell cycle G1

A

Gap 1

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13
Q

cell cycle G0

A

resting

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14
Q

what happens in S phase

A

viral transcription

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15
Q

what is formed after S phase

A

DNA replication proteins (viral DNA replication)

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16
Q

Cyclin D pathway - G0

A

no cell cycle as E2F bound by protein complex (mainly made of Rb)

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17
Q

viral cell cycle

A

E2F switches cell on - cell cycle genes and leads to proliferation
Cyclin D – cyclin dependent kinases, needs phosphorylation of Rb, releases E2F represses
Cyclin E activated
E2F can drive cellular expression

18
Q

Modulation of Apoptosis

A

Normal cells
Cell proliferating – cell is transformed
Permitted by transformation become benign tumour
Local invasion and proliferation
Early metastasis (spreading)
Metastatic cancer and resistance to therapy

19
Q

what leads to appoptosis e.g.

A

loss of pro-apoptotic signals
checkpoint defect
oncogene activation
mutation of DNA damage sensing system

20
Q

what are used to modulate apoptosis

A
  • p53
  • Bcl-2
  • FLICE inhibitory proteins
21
Q

what is P53

A

transcription factor - tumor suppressor activity

22
Q

what happens to P53 if have cancer

A

No human cancer that cell expresses functional P53

23
Q

what activates BH3

A

stress signal

24
Q

what happens when BH3 is activated

A

leads to apoptosis

25
Q

ROS Damage effect of inflammatory response

A

generate radicals, including OH. and NO.

free radicals

26
Q

what does ROS damage

A

> DNA (mutation)
protein (nitration, nitrosation)
RNA
lipids (lipid peroxidation)

27
Q

how do free radicals promote cancer e.g.

A
  • mutating cancer related genes

- activating signal transduction pathways

28
Q

what happens to any cell not expressing P53

A

die

29
Q

what percentage of cancers are caused by viruses

A

15-20%

30
Q

what do viruses that cause cancer have in common

A

all cause chronic infections

31
Q

why do viruses cause cancer

A

don’t on purpose
for them to function - critical viral lifecycle
cause cancer due to the things they need to do to maintain their lifecycle
is a chance outcome

32
Q

epidemiology example

A

hep B causes hepatocellular carcinoma

high links seen in sub-Saharan Africa

33
Q

what is hepatocellular carcinoma

A

primary liver disease

34
Q

why might there be no link of hep B and hepatocellular carcinoma in e.g. spain

A

high cancer
low hep B
- other factors cause cancer e.g. drinking alcohol
- may intervene with vaccines

35
Q

what must stop for cancer to occur

A

stop apoptosis

36
Q

what is Bcl-2 function

A

in mitochondria membrane controls the permeability, when proteins from mitochondria leak into cytoplasm = apoptosis

37
Q

what is p53 function

A

increases mitochondrial membrane permeability

38
Q

what is FLIPS function

A

FLICE inhibitory proteins

surface receptors that transmit apoptotic signals

39
Q

examples of radicals

A

OH.

NO.

40
Q

how does merkel cell virus cause cancer

A

infection in childhood
stay low level as
BUT immunosuppression occurs e.g. age, immunocompromised (AIDS), transplant = increase frequency of replication
virus integrate into DNA - insert randomly into genome
second mutation = helicase inactivation
lead to merkel cell carcinoma

41
Q

how can viruses overcome cells to drive cell cycle

A
  • prevent Rb suppressing cell cycle
    > phosphorylate
    > complex with activating proteins (change Rb from suppressing to activating)
    > lift off promoter
42
Q

what is Rb

A

retinoblastoma - tumour supressor gene

Medical Microbiology (13 decks)

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