Viral Oncogenesis Flashcards
percentage of the association of virus with a given cancer
15% to 100%
what human cancer arises as an acute consequence of an infection
none – latency period between first infection and cancer development can be range from 15 - 40 years
how common are viral infections that are linked to human cancers
extremely common - ubiquitous
is there synthesis of the viral agent within the cancer cells
no
what is mandatory for malignant conversion of a cell in relation to a virus
the virus must act on the host chromosome to cause mutation or the mutation must be within the viral genome
what does it mean for some infectious agents to be indirect carcinogen
they play a role in cells becoming cancerous without actually persistence of their genes within the respective cancer cells
what does it mean for chemical and physical carcinogens to act as mutagens
they cause genetic mutation (usually synergistically with carcinogenic infectious agents)
what are the officially designated human carcinogens by DHHS and what cancers do they lead to?
Hep C - hepatocellular carcinoma
Hep B - hepatocellular carcinoma
HPVs - cervical, anal, and oral carcinomas and maybe non melanoma skin cancers
18.6% of total cancer incidence is due to what 5 viral infections
HBV HCV HPV EBV Helicobacter Pylori
what are some mechanisms done differently in tumor viruses
aberrant cell cycle, block apoptosis, cellular transcription development, chromatin remodeling, inflammation, metastasis, modulating signaling
why is it thought that cancer development by viruses is an accident
it is not smart for virus to produce cancer because the cells in which they transform cannot make more viruses and release them
in cells in which virus transform, what are the hallmarks causing cancer
loss of growth control, reduced adhesion, motility, invasion, ability to form tumors
what do transformed cells (those transformed by virus) usually exhibit
chromosomal aberrations
what type of viruses can transform cells
both DNA and RNA tumor viruses
what happens when tumor viruses integrate their viral genome into the host chromosome?
production of more viruses by host diminishes or becomes absent
what are human oncovirus replication and persistence strategies (hallmarks of cancer)
- find/create conditions for replication (induce the cell cycle, metabolic programming, inducing angiogenesis)
- ensure correct replication (recruit or inhibit DDR)
- maximize virus production (prevent apoptosis until virion matures, immune evasion)
- multiply latent episomes or provirus (cell survival, cell immortalization, cell proliferation)
viral oncoprotein in EBV
EBNA-1
viral oncoprotein in HPV
E6 and E7
viral oncoprotein in HBV
HBx (important because it hits all pathways)
viral oncoprotein in HTLV-1
Tax
pathways that most tumor viruses go through
p53 and Rb
proteins involved in papilloma and polyoma respectively (DNA tumor virus)
papilloma - E6 and E7
polyoma - Large T and small T antigen
proteins involved in adenovirus and BK virus (DNA tumor virus)
adenovirus - E1A and E1B
BK - Large T
proteins involved in SV-40 (DNA tumor virus)
large T
what do DNA Tumor Viruses have in common
have sequences in common –> mutations in these regions abolish transformation capacity
properties of DNA Tumor Viruses
- can transform cells or have lytic life cycle
- often integrate into host genome
- in transformation, often ONLY early genes are transcribed
- these are genes that are also necessary for a PRODUCTIVE infection
1 virus associated STD
HPV
how does HPV cause cancer
HPV infection (0-1yrs) –> low grade dysplasia (1-5 years) –> high grade dysplasia ( 1- 40 years) –> invasive cervical cancer
mechanism of HPV associated carcinogenesis
HPV infection –> viral clearance –> type specific immunity
HPV infection –> viral persistence –> viral clearance –> type specific immunity
HPV infection –> viral persistence –>episomal or integration of viral DNA (overexpression of E6 and E7) –> increased in cell proliferation, decrease in repair –> mutation –> CIN –> invasive cervical cancer
what does E6 and E7 target
p53 and pRb respectively
ultimate B lymphocyte parasite
EBV (HHV4)
symptoms of EBV
greater than 90% of those infected are asymptomatic but do shed for life
what does EBV do
stimulate growth and immortalizes B cells in culture
what carcinomas are EBV associated with
AfBL (african burkitt lymphoma), hodgkins disease, NPC, B cell lymphomas in patients with acquired or congenital immunodeficiencies
what is the virus associated with Kaposi’s Sarcoma
HHV-8 aka KSHV
what is kaposi’s sarcoma
tumor of the blood vessel walls that is usually common in those with HIV – frequently detected in those with AIDS
how does kaposi’s sarcoma present
pink, red, or purple lesions on the skin or mouth
