Lecture 3 (tumorigenic DNA viruses) Flashcards

1
Q

Advantages of using retroviruses to identify oncogenes

A

They efficiently reproduce tumours in experimental animals and transform cells in culture. Also, the small size of the viral genome facilitates isolation of the gene.

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2
Q

Difference between DNA viral oncogenes and RNA viral oncogenes

A

DNA viral oncogenes are usually truly viral. RNA viral oncogenes are usually of cellular origin and cancer arises due to the virus altering the cellular gene.

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3
Q

6 DNA viruses implicated in cancer

A
  • Hepatitis B (Hepadnavirus)
  • SV40 and polyoma
  • Papilloma virus
  • Adenoviruses
  • Herpes virus
  • Pox viruses
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4
Q

Which DNA viruses are implicated in human cancers?

A
  • Hepatitis B
  • Papilloma
  • Herpes virus
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5
Q

Cancer typically arises when a virus infects a species other than…

A

its normal host (block on lysis leads to transformation)

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6
Q

RNA viral family implicated in carcinogenesis (very seldom in humans)

A

Retroviruses

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7
Q

SV40 usually infects monkey cells, which leads to…

A

viral replication → cell lysis → progeny virus released

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8
Q

What can happen if SV40 infects other cells but the support mechanisms are not there to permit cell lysis?

A

Replication is aborted, SV40 interferes with the cell cycle and, in rare cases, can cause cell transformation → cancer

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9
Q

Many tumorigenic viral proteins target…

A

tumour suppressor proteins such as p53 and Rb

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10
Q

Primary site of Hepatitis B viral infection

A

Hepatocytes in the liver

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11
Q

Human Hepatitis B viral infection increases (100-fold) risk of __ in chronically infected individuals

A

liver cancer (hepatocellular carcinoma)

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12
Q

Why is the risk for mutations and oncogene activation increased in chronically HBV infected individuals?

A

Because HBV-infected hepatocytes are destroyed by the immune system and the liver regenerates to replenish the tissue

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13
Q

Examples of other risk factors for liver cancer, besides HBV

A
  • Hereditary haemochromatosis
  • Substance abuse (alcohol/drugs)
  • HCV
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14
Q

HCV-infected individuals also have an increased risk of __

A

Non-Hodgkin’s lymphoma (not understood why)

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15
Q

True or False: The risk for developing liver cancer in individuals with haemochromatosis is higher than in HBV-infected individuals.

A

True

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16
Q

SV40 and polyoma virus induce cell transformation as a result of…

A

stable integration of early region viral DNA, followed by continual expression of viral gene products (which hijack cell cycle progression)

17
Q

SV40 and polyoma virus middle T and large T antigens interact with…

A

cellular proto-oncogene products (src) and tumour suppressor proteins (p53 and Rb)

18
Q

~80% of human cervical carcinomas are caused by…

A

HPV 16, 18 or 26

19
Q

What HPV antigens are expressed in the majority of cervical carcinomas?

A

E6 and E7

20
Q

HPV E6 antigen interacts with __

A

p53

21
Q

HPV E7 antigen interacts with __

A

Rb

22
Q

Quadrivalent recombinant vaccine that targets HPV types 6, 11, 16 and 18

A

Gardasil (aka Silgard) - FDA approved in 2006

23
Q

True or False: The HPV vaccine is only on offer to teenage girls.

A

False

24
Q

Adenoviruses can cause __ in humans

A

respiratory tract infections

25
Q

Two adenovirus early genes implicated in transformation in rat or hamster cells

A

E1A and E1B (interact with Rb and p53, respectively)

26
Q

Human Epstein-Barr virus is strongly implicated in which two human cancers?

A
  • African Burkitt’s lymphoma (ABL)
  • Nasopharyngeal carcinoma (NPC)
27
Q

Why is ABL endemic in sub-tropical Africa?

A
  • co-incident with areas where malaria is widespread
  • malarial infection chronically stimulates immune system, which causes EBV-infected B cells to proliferate & divide
28
Q

Where is NPC most common?

A

Southern China

29
Q

All NPC cases worldwide are associated with __

A

EBV, and express viral proteins

30
Q

Latent EB viral proteins implicated in the transformation process

A

Epstein Barr nuclear antigen (EBNA) and latent membrane proteins (LMPs)

31
Q

Another name for EBV?

A

Human herpes virus 4

32
Q

In recent decades, EBV has also been implicated in…

A

post-transplant lymphoma and Hodgkin’s lymphoma

33
Q

EBV replicates fully in __ cells (typically in nose & mouth)

A

epithelial

34
Q

Chromosomal translocation often seen in Burkitt’s lymphoma

A

Translocation of the c-myc gene into Immunoglobulin locus

35
Q

Most common translocation present in 80% of Burkitt’s lymphoma cases

A

t(8;14)

36
Q

Pox viruses replicate in __

A

cell cytoplasm