Lecture 4 & 5 (tumorigenic RNA viruses)

Question 1

Three families of retroviruses

Answer 1

1. Oncoviruses (oncongenic viruses)
2. Lentiviruses (slow viruses)
3. Spumaviruses (foamy viruses)

Question 2

How do retroviruses replicate?

Answer 2

via a DNA intermediate or provirus which integrates into host DNA

Question 3

What viral protein is important for proviral integration into the host genome?

Answer 3

integrase

Question 4

3 principal viral genes

Answer 4

Gag, Pol, Env

Question 5

What does Gag code for?

Answer 5

the virion’s structural proteins

Question 6

What does Pol code for?

Answer 6

reverse transcriptase enzyme (copies RNA into DNA)

Question 7

What does Env code for?

Answer 7

the virus’s envelope proteins

Question 8

Two groups of oncogenic viruses

Answer 8

Group I: long latency transforming
Group II: acutely transforming

Question 9

How do long latency transforming retroviruses perturb host genome expression?

Answer 9

because of the provirus location in the genome (insertional mutagenesis)

Question 10

Example of a long latency transforming retrovirus

Answer 10

mouse mammary tumour virus (MMTV)

Question 11

Do long latency transforming retroviruses carry an oncogene?

Answer 11

No

Question 12

The most frequent site of ALV DNA integration in lymphomas is between…

Answer 12

exons 1 and 2 of c-myc proto-oncogene

Question 13

MMTV proviral DNA is integrated downstream of __ in mammary carcinoma

Answer 13

int-1

Question 14

Oncogenes discovered by insertional mutagenesis

Answer 14

1. myc (transcription factor)
   - ALV
2. ErbB/EGFR (RTK)
   - ALV
3. int-1 (growth factor)
   - MMTV

Question 15

When ALV infects a cell and by chance integrates close to the src gene, the resulting virus contains part of src gene and is called __

Answer 15

Rous sarcoma virus (RSV)

Question 16

What is the only acutely transforming retrovirus known to carry the src oncogene in addition to its full complement of viral genes (gag, pol, env)?

Answer 16

Rous sarcoma virus (RSV)

Question 17

Acutely transforming retroviruses are derived from…

Answer 17

long latency retroviruses (have transduced a cellular oncogene)

Question 18

How do acutely transforming retroviruses cause cancer?

Answer 18

Due to aberrant expression or qualitative changes to the transduced gene (i.e. the gene that they’ve picked up)

Question 19

What do acutely transforming retroviruses usually require to replicate?

Answer 19

a ‘helper virus’ from Group I

Question 20

Examples of acutely transforming retroviruses and their oncogene

Answer 20

• RSV (src)
• FBJ-MSV (fos, expressed as an independent translation product of full length viral RNA)
• Ab-MuLV (abl, expressed as a gag fusion protein)
• AEV ES4: ErbA (expressed as a gag fusion protein) and ErbB (translated independently from spliced mRNA)

Question 21

What receptor does ErbA encode?

Answer 21

Thyroid hormone receptor

Question 22

__ oncogene is a receptor tyrosine kinase

Answer 22

Kit

Question 23

Differences between retroviral oncogenes (v-oncs) vs cellular oncogenes (c-oncs/proto-oncogenes)

Answer 23

• Much higher level of expression (quantitative change)
• Contain no introns (qualitative change)
• Structural differences e.g. fusion protein with gag
• Point mutations (very common)

Question 24

Point mutation → v-Ras

Answer 24

One amino acid change at position 12 for example causes Ras to be constitutively active (GTP-bound)

Question 25

Mutations in RSV src gene

Answer 25

• Deletion of 19 C-terminal amino acids enhances tyrosine kinase activity
• Several amino acid substitutions will increase the protein activity → increased expression of src