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Cell Bio > 3-viral oncogenesis > Flashcards

3-viral oncogenesis Flashcards

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Biology 101 flashcards
1
Q

all cancers associated with viral infections are…

A

mistakes or byproducts of viral replication or gene expression

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2
Q

viruses that participate in tumorigenesis

A

retroviruses , papillomaviruses

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3
Q

how do viruses cause cancer?

A

inject DNA into cells , cause mutation

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4
Q

what is included in structure of simple retrovirus

A

RNA genome, envelope, Gag, Pol

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5
Q

Envelope consists of

A

surface glycoprotein, transmembrane protein

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6
Q

Pol consists of

A

integrase, reverse transcriptase

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7
Q

Gag consists of

A

Matrix, capsid, nucleocapsid

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8
Q

What is the gene of retrovirus

A

LTR, gag, pol, env, LTR

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9
Q

LTR

A

long terminal repeat that serves as promoter sequences for transcription of the reverse transcriptase gene

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10
Q

where are LTRs

A

3’ and 5’ end

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11
Q

how does retroviruses replicate

A

virus RNA is translated into DNA after entry into host through reverse transcriptase
-the translated DNA is integrated into host chromosome where it remains

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12
Q

steps of retrovirus infection

A
  1. retroviral particle attaches to cell surface
  2. endocytosis
  3. uncoating of nucleocapsid
  4. reverse transcriptase integrates the provirus into the host DNA
  5. assembly of infected mRNA –> proteins
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13
Q

2 classes of retroviruses

A

simple
complex

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14
Q

example of simple

A

feline leukemia

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15
Q

example of complex

A

bovine leukemia

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16
Q

what did hubner and todaro hypothesize

A

-cancer is caused by activation via mutation or inappropriate expression of a normal cellular gene

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17
Q

activated cellular gene

A

oncogene

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18
Q

normal cellular gene

A

proto oncogene

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19
Q

2 mechanisms for simple retroviruses

A

transduced by retroviruses (oncogene capture)
activated by an integrated provirus

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20
Q

what is retroviruses transduce cellular oncogenes

A

-retrovirus combines with oncogene and carries it in the viral genome
-make genome unfunctional and has to give up one of the functional units

21
Q

how does simple retrovirus acquire a cellular proto oncogene

A

recombination

22
Q

what allows simple retroviruses transduce cellular oncogenes

A

requires a helper virus that contains all the functional units to rescue the virus and allow replication

23
Q

essential viral coding sequence is replaced by cell derived oncogene sequence. so these retroviruses are ___________

A

defective in replication

24
Q

how can simple retrovirus transduction cause cancer

A
  1. mutated gene so that the protein is constitutively active
  2. inappropriately expressed or overproduced
25
Q

how do simple retroviruses integrate oncogenes

A

LTR activates oncogene
precursor to transduced oncogenes

26
Q

what indicates that tumors arose from a single cell mutation?

A

in tumors, the provirus is always found at the same site in the cell
-but the retrovirus can be integrated anywhere in the host cell genome

27
Q

what is the site of retrovirus integration?

A

promoter regions or enhancer insertion

28
Q

how do retroviruses integrate at the promoter insertion

A

retrovirus integrates near oncogenes allowing 5’ end or 3’ end of oncogene to fuse with LTR of retrovirus which activates it
-viral and cellular transcripts duse

29
Q

how do retroviruses integrate at the enhancer insertion?

A

-presence of retrovirus will inc. expression of oncogene due to powerful LTR
-viral and cellular transcripts are not fused

30
Q

could these same proto oncogenes be involved in non viral associated cancers

A

yes

31
Q

where do oncogenes activated by simple retroviruses fit in the cell cycle

A

M phase to begin cell cycle
mitogenic signals

32
Q

how do complex retroviruses cause cancer

A

deregulation of host genes involved in proliferation like cytokines and functional inactivation of p53 due to virus in lymphocyte

33
Q

what is unique about complex retroviruses with cancer?

A

viral expression is seen at low levels in lymphocytes but no viral gene expression occurs in the tumor
-there is no virus in tumor

34
Q

what allows complex retroviruses to cause cancer

A

TAX; viral transcriptional trans-activator and functions to make lots of viral RNA

35
Q

TAX affects:

A

-activate transcription
-activate cytokines
-inactivate p53
-cause genomic instability

36
Q

where do oncogenes activated by complex retroviruses fit in the cell cycle ?

A

Simple retroviruses: activate mitogenic signals and start cell cycle –> M phase
Complex: TAX, represses DNA repair and inactivates p53 –> G1-S

37
Q

what are papillomaviruses ?

A

small non-enveloped DNA viruses that contain simple genome
-lytic viruses that normally cause warts can result in invasion cancers

38
Q

what is unique about papillomavirus replication

A

intimately linked to tissue differentiation
-only select viral genes are expressed in cells that are at a specific stage of differentiation
-the terminally differentiated cell is the only cell that produces virus

39
Q

how do papillomavirus cause cancer

A

contain viral genes that sequester tumor suppressor genes (p53, Rb)

40
Q

how do papillomaviruses inactivate p53

A

has E6 that binds to p53 resulting in ubiquitination and degradation
-leads to loss of genome maintenance functions and accumulate mutations

41
Q

how do Papillomaviruses inactivate Rb?

A

has E7 that sequesters Rb allowing constitutive progression in cell cycle
-allows E2f to be constantly free and active

42
Q

papillomaviruses are ___

A

lytic

43
Q

how do papillomaviruses cause cancer

A

presence of a sub genomic segment of papillomavirus DNA (viral promoter E6, E7) which has accidentally integrated into the host DNA and permanently overrides the p53 genome maintenance function without cell lysis ==> cancer

44
Q

where do papillomaviruses deregulate the cell cycle

A

at G1 (Rb) and S phase (p53)

45
Q

how do simple retroviruses cause cancer

A

transduce or insertionally activate cellular genes that lead to cancer

46
Q

how do complex retroviruses lead to cancer

A

trans-activate cellular genes that are both proliferative in function and repress tumor suppressors like p53

47
Q

how do papillomaviruses cause cancer

A

E6 and E7 proteins inactivate host tumor suppressor p53 and Rb proteins

48
Q

viruses provide 2-3 mutations necessary for oncogenic transformation. where do the rest come from?

A

over time because p53 genome maintenance function is lost and mutations accumulate

Cell Bio (17 decks)

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