Ch.3: Tumor Viruses

Question 1

What is a virus composed of?

Answer 1

genetic material (RNA/DNA) enclosed in a protein coat

Question 2

What do viruses do?

Answer 2

generally,
1. Infects/enters a cell
2. Release its genetic material
3. Hijacks cellular machinery to make more copies of itself
4. Assembles new virus
5. Breaks open the cell to release the new virus (in some cases)
6. The new virus can then infect more cells

Question 3

What did Rubin and Dulbecco do?

Answer 3

They showed that RSV transforms cells in culture

Question 4

transformation

Answer 4

conversion of a normal cell into a tumor cell

Question 5

What was some first evidence that a virus can cause cancer?

Answer 5

Peyton Rous and chicken sarcoma virus:
- chicken with sarcoma -> remove sarcoma -> turn sarcoma into filtrate -> inject into young chicken -> young chicken gets sarcoma

Question 6

Properties of transformed cells

Answer 6

1) Altered morphology
2) Loss of contact inhibition
3) Anchorage-independent growth
4) Growth factor independence
5) Immortal growth
6) Tumorigenicity

Question 7

RSV

Answer 7

• a retrovirus (RNA virus)
• lifestyle and structure in slides

Question 8

What does RSV’s extra gene (V-SRC) do?

Answer 8

gives it oncogenic potential

Question 9

hybridization

Answer 9

the process in which two complementary single-stranded DNA and/or RNA molecules bond together to form a double-stranded molecule (dependent on matching base pairs)

Question 10

Potential mechanism of SRC “capture” by virus

Answer 10

look at slide (17)

Question 11

sequence and structure homology between V-SRC and C-SRC

Answer 11

• v-SRC lacks the c-
  terminal domain
  found in c-SRC,
  which is highly
  regulated in normal
  cells
• In normal cells…
  c-SRC is highly
  regulated by the c-
  terminus
• SRC is activated by cell surface receptors in the
  presence of growth factors
• SRC is involved in:
• Cell proliferation
• Cell survival
• Cell motility

Question 12

Acutely transforming
retrovirus

Answer 12

acquire
proto-oncogenes from
genomes of infected host
cells (ex- RSV and SRC)
timescale- days to weeks

Question 13

Slowly transforming
retrovirus

Answer 13

activate
proto-oncogenes in the
host genome by integrating
next to them and altering
their expression patterns
(ex- ALV and MYC)
timescale- months

Question 14

ALV Characteristics

Answer 14

• Almost all B-cell
  lymphomas induced by ALV
  involved viral integration at
  the MYC gene in the host
  genome
• During the course of ALV
  infection of a host, ALV is
  inserted randomly into
  many different genomic
  sites. (different site for
  each cell)
• Most of the time there is
  no effect on the host
  genes. But integration near
  the MYC locus causes
  increased transcription of
  the host MYC gene

Question 15

DNA viruses ___ cancer (Ex: HPV)

Answer 15

induce

Question 16

What do many tumorigenic DNA viruses do?

Answer 16

replicate as
circular DNA episomes, integration into the
host DNA/human chromosomes is rare

Question 17

If viral oncogenes are integrated into the
host genome…

Answer 17

their encoded proteins may be expressed and may interact with proteins of
the host cell

Question 18

What do viral E6 and E7 genes do upon integration?

Answer 18

they inactivate TP53 and RB (tumor suppressors)
- Viral proteins bind to RB
and TP53 proteins, this
allows for the transcription
of genes that promote cell
division (proliferation)

Question 19

What is/does Rb TP53 do?

Answer 19

• they are proteins
• usually inhibit
  cell proliferation and
  ensures cell division is
  tightly regulated (it only
  occurs when necessary)

Question 20

How did we find out that viral E7 inhibits RB? E6 and p53?

Answer 20

• Methods: Human lung cells in culture are infected with different viruses.
  (Levels of phosphorylated RB protein were measured via a Western Blot)
• Results: Levels of phosphorylated RB
  protein decrease in the presence of viral E7
• Interpretation: E7 impairs RB protein stability

(same for E6 and p53)