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1

What is the objective of this lecture?

1. To know the mechanisms by which viruses can cause cancer
2. To know which viruses cause cancer in humans, and how this can be prevented.

2

What are proto-oncogenes that control the growth of cells?

1. myc - transcription factor
2. sis - platelet-derived growth factor
3. erb B - growth factor receptor

3

how do some retroviruses cause cancer in animal?

1. some contain oncogene and express them in infected cells
2. some can insert their promoter into a chromosome and cause expression of regional oncogene

4

p53 protein can be inactivated by

viral protein

5

retinoblastoma protein (pRB) can be inactivated by

viral proteins

6

What are the two viruses that are specific-specific?

1. SV 40 virus
2. Adenoviruses (various serotypes)

7

SV 40 virus

1. a primate virus that causes cell transformation and cancer in rodents
2. transforms human cells to a malignant state
3. express T antigen which inactivated p53 and pRB

8

Adenovirus

a group of human viruses, some of which cause cell transformation and cancer in rodents, but only cause colds and sore throats in people

9

What are the 5 viruses that cause cancer in humans?

1. human papillomaviruses
2. Epstein-Barr virus
3. Hepatitis virus (HBV and HCV)
4. Human T-cell lymphotropic virus (HTLV-1 and HTLV-2)
5. Kaposi sarcoma herpes virus (KSHV, HHV8)

10

Human papillomaviruses

1. low risk types, such as HPV-2 and HPV-4 cause warts
2. high risk types, such as HPV-16 and HPV-18 cause squamous cell carcinomas of the cervix, penis, and orpharynx

11

In HPV, E6 and E7 genes function in same way as

T antigen of SV40

12

In HPV, the progression to carcinoma is

slow, requiring many years

13

HPV vaccines consist of

empty virus capsids

14

HPV vaccines reduce the incidence of

cervical intraepithelial neoplasia (CIN)

15

What is a herpes virus that causes mononucleosis?

EBV

16

what is a herpes virus associated with childhood lymphoma (Burkitt's) in parts of Africa and in patients with AIDS?

EBV

17

What is the characteristics of Burkitt's lymphoma?

1. tumors express a latent viral antigen of uncertain function
2. have a translocated oncogene (myc) which is overexpressed.

18

EBV is also associated with

naso-pharyngeal cancer in Asia

19

What are the co-factors of EBV infection?

malaria infection in Africa and food preservatives in Asia

20

What do hepatitis viruses (HBV and HCV) cause?

chronic hepatitis that predisposes to cirrhosis and liver cancer after many years

21

Hepatitis is prevalent in

Africa and Asia

22

What is the characteristics of Human T-cell lymphotropic virus (HTLV-1 and HTLV-2)?

1. RNA virus
2. but with no oncogene

23

What is the molecular basis of HTLV?

tax gene causes overexpression of interleukin-2 and the receptor for interleukin-2. other proteins dysregulate RNA metabolism
3. blood borne

24

What does HTLV lead to?

leukemia and lymphoma

25

HTLV is prevalent

in Caribbean

26

Kaposi sarcoma herpes virus (HHV8) is associated with

Kaposi's sarcoma in pts with HIV. (unknown mech)

27

all of the cancerous features (abnormal chromosomes,immortal, not contact inhibited etc) can be induced experimentally by

viruses

28

sis (protooncogenes)

platelet derived growth factor

29

ras (protoconcogenes)

signal transduction from surface receptors

30

Inactivation of p53 or Rb allows cells

to proliferate and accumulate other mutaitons