What can cancer causing viruses provide us?
discovery of proto-oncogenes, tumor suppresor proteins and appreciation that cancer can be studied at the single cell level
What was the first oncogenic virus?
rouse sarcoma virus from chikcens
What is the advatnage of using tissue cultures?
allows study of regulatory evetns at the cellulara and sub-cellular levels
What is the disadvantage of using tissue cultues?
does not always correspond to tumor formation in animals
What is the qunitive pheotype that can be observed from a tissue cultue infection by tumor viruses?
focus formation on a perti dish and the cell transofrms
What happens to transformed cells?
The cells beomce refractory, long & stretched out. Cells lose their contact inhibition and use single microscopy & lead to altered microscopy
What happens to transformed cell?s
altered morphology and loss of contact inhibition decreaed need of growth factor requienct and loss od dependce on achorage for growth
What happens in an altered morphology?
Cells appear rounded and refractile
What happens with a loss of contact inhibition?
cell can grow over one another or over normal cells
Where did the RSV virus evolve from?
The RSV evolved from the ALV after an addtion of a src viral gene
How did the RSV get the oncogence src gene?
captuated from a c-src by a trasctioipn error after teh ALB integratios the c-src is misktaning transcotoiung and pushing into a RSV virion
What normally inhibits the src protin?
The c-terminal region normally autohinits the src protein
What happens in the v-src?
The c-terminal region is truncated and thus cases the auto-inhibitory domain to be shrunk which thus causes the constitutively active src protein to be on
What are the two types of retroviruses?
Acute and chronic transoforming
What are the features of an acute transforming retrovirus?
rare in nature, cause tumors 2-4 weeks after infection. 100% efficient. transfmor in cell culture carry an incogene most are replication defective, the integration site is random. Tumor formation is not dependent on site of integration thus many target ce
What is the qualitative change that occurs with acute transforming returoviruses?
structural change or mutation in the gene such that the prptein product become constitutively activated
What is the quanititave change in acute transforming retroviruses?
expression of the gene is placed under the control of a viral LTR
What are the features of chronic transforming retroviruses?
do not carry oncogenes, the virus is replication competntn, casues cancer after a long latent period, extremely inefficnt in terms of replicating./ Retrovirus integrates clost to or within an important grwoth regulatory gene (proto-oncogene) and altegers
What are the requirements for a virus to cause cancer?
virus persists in tumor cells as DNA, virus maintains the expression of a viral or host oncogene
Why type of infection is needed for DNA tumors?
non-productiveinfections
What happens to small DNA tumor viruses?
integrate into host DNA
What happens to large DNA tumor viruses?
establish latency as episomes
Whick virus cause cervial carcinomas?
HPV16 HPV18
What causes merkel cell carcinoma?
MCV
Which hepatitis viruses cause hepatocellular carcinoma?
HBV, HCV
Which herpes viruses cause cancer?
EBV burkitt's lymphoma and nasopharyngeal carcinoma and KSHV kaposi's sarcoma awith the endothelial cell
Which retrovirus causes cancer?
HTVL-1
What is the main disease that all acute infections of herpesviruses give?
mononucleosis
Which cells do herpesviruses infect?
B lymphocytes and epithelial cells
What are the two types of cancers associated with EBV?
Burkitt's lymphoma and nasopharyngela carcinoma
What type of maliganancies are EBV-associated cancers?
monoclonal and hae long latent periods
What are the three EBV proteins needed for transformation?
EBNA-2, LMP-1, and EBNA-1
What does EBNA-2 do?
transcriptional activator that orchestrates latent gene expressoin and activate LMP-1. EBV nuclear antigen -2
What does LMP-1 do?
transform permanent cell lines and induce B cell lymphomas in transgenic mice latent membrane protein -1
What does EBNA-1 do?
reuited for replicating latent episomal genome, tethers genome to host chromosome
What is the mechanism of oncogenicity by EBV?
transformation associated with EBV. c-myc is overexpressed by one of two mechanism. EBNA 2 directly transactivated it or C-myc is translocated next to a strong cellular promoter. Then NF-kB is constitutively actiavted by LMP-1 and stops apoptosis
How does LMP1 cause oncogeneisis?
LMP1 the oncoprotein mimns the CD40 and stays constitutively active to keep growth on of infected B cells.
What does CD40 normally do?
regulated gene transcrition for cell activation, growth and survival
Explain the productive cycle of genes for the KSHV?
IE genes make transcription factors and then make delayed early genes for vDNA rpelciton. This leads to chronc cell growth aas the latent oncogens are turned on by the delayed early genes
What are the two mechanisms of transformation by viral proteins?
permanent activation of signal transduction caascades and disruption of the circuits that regulate cell cycle progression or apoptosis
Whare tare the subclasses of viral transofrming proteions?
growth factor increase, growth factor receptiosn, intracellualr transducers, intracellular receptors, DNA-repaire proteins, cell-cycle control protein and anti-apotosis protins.
What can viral oncogenes be?
mutatnt homologs of cellualr genes, wild-type homologs of cellular genes that are over-expressed or novel viral genes