6 - Tumor Viruses Flashcards
What is the genetic origin of cancer attributed to?
oncogenic viruses
What is significant about the Rous sarcoma virus?
first discovered virus that can induce sarcomas in chickens
What type of genome (RNA or DNA) does the Rous Sarcoma Virus (RSV) have?
RNA
What are transforming retroviruses?
cancer-causing single-stranded RNA virus that uses reverse transcriptase to make ssDNA into dsDNA which integrates into host genome
If a virus wants the cell to move, how will it make the cell do this function?
induce cytoskeletal rearrangement = cells start to move and grow »_space;> mobility
What is the key characteristics of the retrovirus life cycles that relates to cancer?
genome integrates and recombines with the host genome
How can viruses be passed onto the daughter cells?
when cells undergo cell division = viruses will multiply and split into daughter cells
How do viruses disrupt/cause cancers?
breaks host DNA »_space;> inserts viral DNA after an active promoter = CAN activate genes that should be off OR deactivate genes that should be on (ie: tumor suppressor genes) | can insert viral DNA in non-protein encoding gene
What are the 2 hallmarks of cancer?
uncontrolled cell division | immortality = doesn’t die (as a population)
What are the mutations of most tumors?
mutated proto-oncogenes
How many mutations does a proto-oncogene need before the cell loses control?
one
How many mutations does a tumor suppressor gene need before the cell loses control?
two
Are all retroviruses, transforming retroviruses?
no
What are the 2 goals tumor viruses reach for?
cell survival | proliferation
What are 5 altered properties of a transformed cell due to transforming retroviruses?
loss of growth control (loss of contact inhibition in cultured cells) | tumor formation | mobility | reduced adhesion | chromosomal aberrations
What are the 2 mechanisms of gene activation by retroviral insertion?
promoter insertion | enhancer insertions
What does the src gene cause? Is this gene normal?
sarcomas | normal in all cells
How can a virus convert a proto-oncogene into an oncogene such as in the case of src?
by altering the gene sequence so it codes for a protein with abnormal activity | brought under control of powerful promoters or enhancers in the viral genome
What is the purpose of the src gene?
involved in cell division
Which cells will respond to a growth factor?
only those that have the receptor for the growth factor
What was the first tyrosine kinase discovered and in what?
src gene in chickens
Do viruses always insert their genome in the same sites in every cell?
not always
What percent of cancers are associated with viral infections?
15% (number changes)
What are the 4 ways viruses can give rise to tumor cells?
genetics | disrupt host gene | bring in own viral genes that can induce neoplasia | immune suppression
What is the “hit and run” method of virus that can induce neoplasia?
virus leaves a mutation in the genome of a normal cell but the virus is not there anymore
What is insertional mutagenesis?
virus DNA inserted in the host chromosome alters or destroys normal gene expression
What can insertional mutagenesis cause?
immune suppression
What are the most common types of papillomaviruses?
16 and 18 = transforms human keratinocytes
What is the function of the HPV viral protein E2?
sticks to spindles when the cells divide so it takes a ride into the daughter cells
What do at least 50% of cancers have mutated?
p53
What is the role of p53?
guardian of the genome | inhibits cell cycle and induces apoptosis
How can viruses inhibit p53?
some viral proteins can act on and inhibit p53
What is E2F? Is it usually on or off?
transcription factor for cell cycle genes | usually off
What is Rb?
discovered in retinoblastoma
What is the function of Rb?
always active | binds and sequesters E2F (off) = no cell cycle genes (like cyclin)
How is E2F activated?
phosphorylate Rb = changes shape and becomes inactive »_space;> releases E2F = activated E2F
What percent of people are infected with Epstein-Barr Virus?
95%
What is HBV?
Hepatitis B virus | goes into liver and causes inflammatory response
What are the 3 anti-oncogenes?
loss-of-function mutations | retinoblastoma (Rb) | p53