Oncogenic Viruses

Question 1

What percentage of cancers are caused by viruses?

Answer 1

15-20% of cancers are caused by viruses

Question 2

Viruses are the leading cause of what forms of cancer?

Answer 2

Cervical and liver cancer

Question 3

What are three general pathways by which viruses can induce cancer?

Answer 3

(1) viruses can activate pathways that stimulate cell growth and proliferation.
(2) Viruses can release cell cycle from normal controls
(3) Cellular destruction leads to unplanned regeneration

Question 4

What are the known human cancer causing viruses?

Answer 4

(1) Human T lymphotropic virus-1 (HTLV-1)
(2) Human herpes virus-8 (Kaposi’s sarcoma)
(3) Epstein-Barr virus (EBV)
(4) Human papilloma virus (HPV)
(5) Hepatitis B virus (HBV)
(6) Hepatitis C virus (HCV)

Question 5

What are v-oncogenes?

Answer 5

Viral oncogenes that are derived from c-oncogenes (proto-oncogenes).

Question 6

How did viruses acquire v-oncogenes?

Answer 6

Probably during viral genome integration into a host genome (retrovirus)

Question 7

What are the three groups of oncoviruses?

Answer 7

(1) transducing oncoviruses
(2) Nontransducing oncoviruses
(3) Nontransducing long latency oncogenic viruses.

Question 8

What are the characteristics of transducing oncogenic viruses?

Answer 8

They contain v-oncogene, have a 100% rate of tumor formation, and form tumors within a matter of days.

Question 9

What are the characteristics of Non-transducing oncogenic viruses?

Answer 9

They do not contain an oncogene.
However they can activate c-oncogenes.
They have a high rate of tumor formation.
They take weeks to months to form tumors.

Question 10

What are the characteristics of non-transducing long latency oncogenic viruses?

Answer 10

They usually contain a v-oncogene unrelated to c-oncogenes.
They cause tumors in less than 5% of infected cells.
They take months to years for tumors to develop

Question 11

How can tumor viruses use signaling pathways to stimulate tumor formation?

Answer 11

They can activate, through dysregulation of kinase cascades, signal pathways that stimulate proliferation.

Question 12

What is one of the main differences between v-oncogenes and c-oncogenes?

Answer 12

v-oncogenes are constitutively active.

Question 13

What is insertional activation?

Answer 13

It is mechanism of transformation used by non-transducing oncogenic viruses whereby the viral genome integrate into the host genome. Once in the host genome, overactive viral gene promoters cause the over expression of c-oncogenes.

Question 14

What proportions of liver cancer are caused by HCV/HBV?

Answer 14

80%

Question 15

What proportion of cervical carcinomas are caused by viruses (HPV)?

Answer 15

Almost all cervical carcinomas are caused by HPV.

Question 16

What are immortalized cells?

Answer 16

They are cells that retain normal characteristics except that they will proliferate indefinitely.

Question 17

What are transformed cells?

Answer 17

Immortalized cells that also (1) have no need for growth signals, (2) loss of contact inhibition (3) anchorage independent (4) Appear round rather than their normal shape, (5) may cause tumors if injected into animals.

Question 18

What is the only example of a long latency oncogenic retrovirus that effects humans?

Answer 18

HTLV-1

Question 19

How does HTLV-1 transform cells?

Answer 19

Tax (a viral gene) appears to stimulate Ikk which then degrades IkB. This frees transcription factor NFkB to enter the nucleus and induce cell proliferation.

Question 20

How does EBV cause cancer?

Answer 20

It contains the LMP-1 oncogene which functions as a constitutively active growth factor receptor.

Question 21

What cancers are caused by EBV?

Answer 21

Burkitts lymphoma
Hodgekins lymphoma
posttransplantational lymphoma
Nasopharyngeal carcinoma

Question 22

What cancers are caused by KSHV (HHV-8)?

Answer 22

kaposi’s sarcoma (lymphatic endothelial cancer), Pleural effusion lymphoma, Castleman’s disease (Lymph node tumors, not necessarily a cancer)

Question 23

How does KSHV cause cancer?

Answer 23

(1)expresses cytokine and chemokine (2)homologs.
Inhibits apoptosis
(3)expresses vGCPR which is constitutively active.

Question 24

What is Simian virus 40 (SV40)?

Answer 24

SV40 is a DNA polyoma virus that causes cancer in animal models but not in humans.

Question 25

How does SV40 cause cancer?

Answer 25

SV40 has a t antigen that alters and prolongs the half-life of phosphorylation events thereby stimulating division in cells.

Question 26

Does SV40 lead to cancer in humans?

Answer 26

Probably not (at least for now based on current knowledge)

Question 27

How do HPVs cause transformation (generally speaking)?

Answer 27

HPV dampens tumor suppressors such as p53 and Rb.

Question 28

What are the low risk forms of HPV?

Answer 28

HPVs 6 and 11 are considered low risk variants

Question 29

What are the High risk forms of HPV?

Answer 29

HPVs 16, 18, and 25 are considered high risk

Question 30

How specifically do HPVs cause cancer?

Answer 30

HPV contains proteins E6 and E7 which bind and inhibit tumor suppressors (P53 and Rb respectively). This happens when abnormal integration of the viral genome causes downregulation of E2, which normally controls E6 and E7.

Question 31

How does KSHV disrupt the cell cycle?

Answer 31

KSHV alters cell cycle control by expressing its own v-cyclin, which is resistant to CDK inhibitors when bound to CDK.

Question 32

How do HBV/HCV lead to transformation?

Answer 32

HBV/HCV cause hepatocellular carcinoma by causing chronic long term inflammation and cellular damage, the result of this is sustained proliferation of hepatocytes which may lead to malignant transformation.

Question 33

How does EBV initiate transformation?

Answer 33

EBV encodes proteins that lead to the immortalization of of B cells. Immortalized B cells that undergo a translocation that puts c-myc under a very strong Ig heavy chain promoter. This can lead to cancer fromation.