Viruses and cancer Flashcards
Two ways that retroviruses can causes cancer
- Acquire a cellular gene in their genome; often this gene was altered by mutations, insertions or deletions. The expression of this mutated gene in the infected cell became regulated by the viral promoter which resulted in its overexpression
- Retrovirus to insert itself into DNA such that the viral promoter or enhancer caused the dysregulated expression of a cellular proto-oncogene
Two retrovioruses (RNA) that cause cancer in humans
Human T cell leukemia virus (only type 1)
Hepatitis C
DNA Viruses that cause cancer in humans
- Two herpes viruses: Epstein-Barr virus, and Human herpes virus 8
- HPV
- The hepadnavirus-hepatitis B virus
- polyomavirus-Merkel cell polyomavirus
Mechanisms of viral cancer
Viruses target cells that they can shift into replication
They also reduce/destroy tumor suppressors or pro-apoptotic genes, like p53
Two proteins that are commonly inactivated in viral cancers are
Rb and p53
What is HTLV-1
Human T-Cell Lymphotropic Virus 1 (HTLV-1) - a retrovirus that causes adult T cell leukemia/lymphoma, a clonal cancer of mature CD4+ T cells
Two proteins of HTLV-1 that have been implicated in the progression to cancer and what they do
Tax increases the proliferation of the infected cell
HBZ and Tax can both, by indirect means, block the function of p53
Cancer forms when the virus deletes the tax gene, because immune system will remove cells that exhibit cells with tax
What two viruses cause hepatocellular carcinoma (HCC)
DNA hepadnavirus, Hepatitis B Virus and a Flavivirus, Hepatitis C Virus
How HCV and HBV can cause cancer
In HBV and HCV infection, there is increased cell turnover caused by immune clearance of infected hepatocytes. Any time there is increased cell turnover, there is always the possibility of mutation.
In addition, the immune response to these chronic infections results in a steady state of inflammatory mediators being released from these immune cells. It is believed that the reactive oxygen species (ROS) released in this environment contributes to DNA mutagenesis.
There is some indication that the X protein of HBV can activate some proto-oncogenes and downregulate genes controlling apoptosis
What proteins of HPV allow it to cause cancer
viral protein E7 binds to Rb which releases E2F resulting in the cell entering the cell cycle
E6 binds and activates a ubiquitin ligase that causes the ubiquitin-mediated degradation of a lot of proteins but most notably p53.
E2 regulates the expression of E6 and E7
Does herpesvirus use viral DNA polymerase
No, It uses the cells polymerase when the cell divides.
Main characteristic of Burkitt lymphoma (BL)
translocation of the c-myc locus to the immunoglobulin locus
Types of BL
endemic, sporadic and immunodeficiency-associated
Most common oncogene of HHV8, where is it found
LANA, found in spindle cell
