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BIO 435: Virology > Oncogenic Viruses > Flashcards

Oncogenic Viruses Flashcards

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1
Q

What is the difference between oncolytic vs oncogenic?

A

oncolytic used for cancer treatment

oncogenic is cancer causing virus

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2
Q

What are the causes of cancer?

A

carcinogen, UV radiation, viruses, genetic predisposition, environmental/occupational, random mutations

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3
Q

What are the molecular mechanisms of cancer?

A

Mutations

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4
Q

How can you prevent cancer?

A

sunscreen
limit carcinogen exposure
vaccination against oncogenic viruses (HPV, Hep B)
antivirals if no vaccination (Hep C)

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5
Q

How is cancer a multi-step process?

A

Cancer develops from cells that have acquired mutations.

These mutations ultimately lead to uncontrolled cell growth

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6
Q

What are the characteristics of cancer cells?

A

bypass apoptosis signals for cell death

circumvent the need for growth signals bypass growth signals needed for division so they can constantly divide

escape immunosurveillance bypass immune response

(tumors) command their own blood supply angiogenesis

may metastasize move to different body locations

lose tumor suppressor gene functions (example p53)

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7
Q

What is p53?

A

Tumor Suppressor Genes that controls when cells divide,
- cancer cells prevent p53 from functioning properly

-p53 acts at G1 to S phase checkpoint to ensure DNA is right before DNA replication
if irreparable then p53 initiates apoptosis

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8
Q

What is cancer?

A

a term for diseases in which abnormal cells divide without control.

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9
Q

What is an oncogene?

A

gene that has the potential to convert a normal cell to a cancerous or transformed cell

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10
Q

What is a Proto-oncogene?

A

cellular genes that promote the normal growth and division of cells (they can be converted to cancer causing oncogenes when dysregulated)

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11
Q

What is a Viral oncogene (v-onc)?

A

a viral gene responsible for the oncogenicity of the virus

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12
Q

What are Tumor suppressor genes?

A

genes that regulate and coordinate the cell cycle and cell division. These genes cause cancer when they are turned off.

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13
Q

What is Cell transformation?

A

changes in the morphological, biochemical, or growth properties of a cell.

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14
Q

What is a Benign tumor?

A

cease to grow in the body after reaching a certain size and generally do no harm

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15
Q

What is a Malignant tumor?

A

grow and divide indefinitely and impair the normal function of organs and tissues

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16
Q

What is Metastasis?

A

when a cell or clump of cells separates from a tumor and spreads to another location.

17
Q

What are the Two main ways that viruses transform cells (1st step in cancer development)?

A
  1. By activation of cellular signal transduction cascades

2. Interference with the cell cycle controls

18
Q

How do oncogenic viruses cause cancer?

A

by inducing changes that affect the processes that control cell proliferation

19
Q

How can Proto-oncogenes be converted to oncogenes?

A

Movement of DNA within the genome: if it ends up near an active promoter, transcription may increase

Amplification of a proto-oncogene: increases the number of copies of the gene

Point mutations in the proto-oncogene or its control elements: causes an increase in gene expression

20
Q

How can translocation convert a proto-oncogene to an oncogene?

A

movement of proto-oncogene so that it’s under influence of different promotor

21
Q

How can gene amplification convert a proto-oncogene into an oncogene?

A

having multiple copies of proto-oncogene instead of just 1 = more protein made

22
Q

How can point mutations convert a proto-oncogene into an oncogene?

A

mutation in gene = hyperactive protein production

mutation in promotor = normal growth stim hormone in excess = excess protein production

23
Q

How can conversion of Ras proto-oncogene to an oncogene leads to uncontrolled cell growth?

A

Normal Cell Growth Process:

  1. Signal (growth factor)
  2. Transduction (relay proteins)
  3. Response (mitosis)

Relay protein RAS is G protein

  • in normal cell it switches from on/off state
  • usually in off state (bound by GDP)

Mutation in RAS causes RAS to be constantly bound by GTP (unable to bind GDP) = constant ON state

  • constant binding by GTP causes constant transduction by relay proteins = constant gene expression for protein that stimulates cell cycle (mitosis)
  • don’t need growth factor signalling at receptor
    “Stepping on the gas”
24
Q

What is an example of a tumor suppressor gene?

A

Tumor-suppressor proteins (p53)

  • Repair damaged DNA
  • Control cell adhesion
  • Inhibit the cell cycle in the cell-signaling pathway
  • Induce apoptosis if damage irreparable

Some of the DNA tumor viruses interfere with the functions of tumor
- suppressor proteins (p53 and Rb)

25
Q

How can a defective or non-functional p53 lead to uncontrolled cell growth?

A

damage to DNA from UV light causes signal transduction cascade that activates p53

p53 binds DNA at promotor upstream of gene

  • cause expression og genes that repair damage to DNA
  • inhibits cell cycle during repair
  • can induce apoptosis if can’t repair

mutation causes p53 to be inactive

  • p53 can no longer stop the cell cycle so damaged DNA gets replicated
  • “putting the brakes on”
26
Q

Cancer cells are first transformed. What are some characteristics of transformed cells?

A
  1. Immortal: can grow indefinitely (can grow in culture forever)
  2. Don’t require serum as much (don’t require as much growth factors in culture)
  3. Normal cells grow to certain density then stop, cancer cells have high saturation densities (don’t stop)
  4. Anchorage independent (can grow in soft agar)
27
Q

In what ways do viruses cause cancer?

A
  1. Introduction of an oncogene (v-onc) into a cell
  2. Activation of a proto-oncogene
  3. Inactivation of a tumor suppressor protein
28
Q

How does viral introduction of an oncogene into a cell cause cancer?

A
  • carry own oncogene (v-onc) in their viral genome
  • transducing retroviruses (exception to rule)
  • rapid transformation in the infected cells
  • always cause cancer
29
Q

How does viral activation of a proto-oncogene cause cancer?

A
  • don’t carry own v-onc
  • Non-transducing retrovirus
  • integration into host genome (proviral DNA)
  • where the virus integrates influences whether or not it will contribute to cancer (eg. integrate into p53 gene knocks it out)
  • don’t always cause cancer
30
Q

How does viral inactivation of a tumor suppressor protein cause cancer?

A

inactivation of p53 results in no longer being able to regulate cell division
- DNA tumor virus (eg. HPV)

31
Q

What are the Molecular Mechanisms of How Retroviruses Can Cause Cancer?

A
  1. Integration of proviral DNA containing a v-onc (oncogene is part of virus) (transducing)
  2. Insertional activation of a proto-oncogene (non transducing)
32
Q

Who were Michael J. Bishop and Harold E. Varmus?

A

Discovered that the src gene of Rous Sarcoma Virus (RSV) is found in the normal DNA of chickens

Their work demonstrated that some oncogenes are cellular genes that were hijacked by viruses

33
Q

How does Rous Sarcoma Virus (RSV) cause cancer?

A

Integration of proviral DNA containing a v-onc
(virus brings the oncogene into the cells)

Rous Sarcoma virus has extra gene in genome
SRC - sarcoma gene

BIO 435: Virology (18 decks)

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