Small dsDNA Viruses

Question 1

Name some major cellular pathways which can be disturbed in order for cells to be tumorigenic

Answer 1

Cell cycle
Protein synthesis
interferon and inflammatory response
DNA repair
Apoptosis

Question 2

Name some oncogenic viruses

Answer 2

EBV
HepB (HBV)
HTLV-1
HPV
HepC (HCV)
KSHV
MCV

Question 3

How many cancers are estimated to be caused by viruses?

Answer 3

One in five - 20%

Question 4

Which virus family was studied in class as the typical small dsDNA?

Answer 4

Polyomaviridae - Polyomavirus

Question 5

What does polyomaviridae do? How?

Answer 5

Polyomaviridae transform cells via T antigens which regulate the cell cycle.

Question 6

What are biotech applications of the polyomavirus?

Answer 6

SV40 T antigens are used as an oncogene to transform non-permissive cells in vitro

Question 7

Describe the polyomavirus genome

Answer 7

It is a small dsDNA which is wrapped around nucleosomes as a torodial coil. It is a circular strand which looks like a plasmid with gene expression in two phases; early and late.

Question 8

Which histones does polyomavirus use?

Answer 8

H2A, H2B, H3, and H4

Question 9

Describe polyomavirus replication

Answer 9

Attachment and endocytosis
Virion is rearranged by disulfide isomerases in the ER
Misfolded virion in the cytoplasm
Misfolded virion loses VP1 in low calcium conditions of cytosol
DNA travels to nucleus
Early genes are transcribed (LT and sT)
Replication of DNA in the nucleus
Transcription of late genes for structural proteins (VP1, VP2, adn VP3)
Assembly in viral factories
Virions released by lysis

Question 10

How does the polyomavirus get to the edge of the host cell to exit?

Answer 10

Possibly via Agno protein as a shuttle

Question 11

Describe the SV40 antigens and their purpose.

Answer 11

LT (large) and sT (small) are involved in virus replication and regulation of host cycle and perturb multiple cell pathways.

Question 12

How does SV40 create transformed cells?
On what does it’s method depend?
In what does it result?

Answer 12

Malignant transformation only occurs if SV40 integrates into the host genome or when SV40 DNA remains episomal with very little cell lysis during infection.
It is cell type specific.
Pleiotropic effects on cell behavior

Question 13

What boxes do cells have to check off in order to be able to become neoplastically transformed?

Answer 13

Immortalization
Growth in low serum
Saturation density overgrowth
Anchorage independence
Ability to form tumors in animals following injection of transformed cells