Lecture 3 (tumorigenic DNA viruses) Flashcards
Advantages of using retroviruses to identify oncogenes
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.
Difference between DNA viral oncogenes and RNA viral oncogenes
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.
6 DNA viruses implicated in cancer
- Hepatitis B (Hepadnavirus)
- SV40 and polyoma
- Papilloma virus
- Adenoviruses
- Herpes virus
- Pox viruses
Which DNA viruses are implicated in human cancers?
- Hepatitis B
- Papilloma
- Herpes virus
Cancer typically arises when a virus infects a species other than…
its normal host (block on lysis leads to transformation)
RNA viral family implicated in carcinogenesis (very seldom in humans)
Retroviruses
SV40 usually infects monkey cells, which leads to…
viral replication → cell lysis → progeny virus released
What can happen if SV40 infects other cells but the support mechanisms are not there to permit cell lysis?
Replication is aborted, SV40 interferes with the cell cycle and, in rare cases, can cause cell transformation → cancer
Many tumorigenic viral proteins target…
tumour suppressor proteins such as p53 and Rb
Primary site of Hepatitis B viral infection
Hepatocytes in the liver
Human Hepatitis B viral infection increases (100-fold) risk of __ in chronically infected individuals
liver cancer (hepatocellular carcinoma)
Why is the risk for mutations and oncogene activation increased in chronically HBV infected individuals?
Because HBV-infected hepatocytes are destroyed by the immune system and the liver regenerates to replenish the tissue
Examples of other risk factors for liver cancer, besides HBV
- Hereditary haemochromatosis
- Substance abuse (alcohol/drugs)
- HCV
HCV-infected individuals also have an increased risk of __
Non-Hodgkin’s lymphoma (not understood why)
True or False: The risk for developing liver cancer in individuals with haemochromatosis is higher than in HBV-infected individuals.
True
SV40 and polyoma virus induce cell transformation as a result of…
stable integration of early region viral DNA, followed by continual expression of viral gene products (which hijack cell cycle progression)
SV40 and polyoma virus middle T and large T antigens interact with…
cellular proto-oncogene products (src) and tumour suppressor proteins (p53 and Rb)
~80% of human cervical carcinomas are caused by…
HPV 16, 18 or 26
What HPV antigens are expressed in the majority of cervical carcinomas?
E6 and E7
HPV E6 antigen interacts with __
p53
HPV E7 antigen interacts with __
Rb
Quadrivalent recombinant vaccine that targets HPV types 6, 11, 16 and 18
Gardasil (aka Silgard) - FDA approved in 2006
True or False: The HPV vaccine is only on offer to teenage girls.
False
Adenoviruses can cause __ in humans
respiratory tract infections
Two adenovirus early genes implicated in transformation in rat or hamster cells
E1A and E1B (interact with Rb and p53, respectively)
Human Epstein-Barr virus is strongly implicated in which two human cancers?
- African Burkitt’s lymphoma (ABL)
- Nasopharyngeal carcinoma (NPC)
Why is ABL endemic in sub-tropical Africa?
- co-incident with areas where malaria is widespread
- malarial infection chronically stimulates immune system, which causes EBV-infected B cells to proliferate & divide
Where is NPC most common?
Southern China
All NPC cases worldwide are associated with __
EBV, and express viral proteins
Latent EB viral proteins implicated in the transformation process
Epstein Barr nuclear antigen (EBNA) and latent membrane proteins (LMPs)
Another name for EBV?
Human herpes virus 4
In recent decades, EBV has also been implicated in…
post-transplant lymphoma and Hodgkin’s lymphoma
EBV replicates fully in __ cells (typically in nose & mouth)
epithelial
Chromosomal translocation often seen in Burkitt’s lymphoma
Translocation of the c-myc gene into Immunoglobulin locus
Most common translocation present in 80% of Burkitt’s lymphoma cases
t(8;14)
Pox viruses replicate in __
cell cytoplasm