Oncogenic Viruses Flashcards
1
Q
oncogenic virus overview
A
- no characteristic shape, genome, or mechanism
- no characteristic target cell, patient, or pathway
- animal models are not reliable predictors of human effects
2
Q
features of human cancer cells
A
- make tumors if transplanted to animals
- undifferentiated
- immortal
- not contact inhibited
- resistant to apoptosis
- abnormal chromosomes
- all of these features can be induced experimentally by viruses
3
Q
myc
A
-TF
4
Q
src
A
-membrane signaling of GF binding
5
Q
ras
A
-signal transduction from surface receptors
6
Q
sis
A
-platelet derived GF
7
Q
erb B
A
GF receptor
8
Q
fms
A
GF receptor
9
Q
LMO2
A
hematopoiesis
10
Q
cell cycle control
A
- by p53- stops cell cycle for repair or causes apoptosis
- Rb- blocks E2F, which would promote cell cycle if not blocked
- inactivation of either leads to proliferation and accumulation of mutations
11
Q
oncogenes are overexpressed in some human cancers
A
- AML- mos
- CML- abl
- APL- fes
- ALL- LMO2
- ovarian cancer- myb
- breast cancer- her2neu
- by amplification, mutation or translocation
12
Q
p53
A
- often mutated in cancer
- breast, bladder, prostate, liver, lung, skin, colon
- Rb may also be mutated
- DNA tumor viruses can target p53 and pRB
13
Q
cell transformation
A
- can be caused by RNA and DNA viruses
- RNA oncogenic viruses carry activated oncogenes, or insert their promoter and activate and oncogene
- DNA oncogenic viruses degrade cell cycle genes
14
Q
oncogenic viruses are species specific
A
-1955-inactivated polio vaccine
1960- live attenuated vaccine from monkey kidney cells
-by sept 1961, 60% of pop vaccinated
-found that SV40 virus had contaminated some vaccines
-causes cancer in hamsters
-transforms human cells to malignant but doesn’t cause cancer
-immunized children shed virus for several weeks in stool
-T antigen inactivates p53 and Rb
-no human tumors found to have this.
15
Q
adenovirus
A
- causes cold and cough in humans
- causes cancer in rodents
- E1A and B analogous to T antigen and always expressed in transformed cells
16
Q
only example of non species specificity
A
- gene therapy viruses can have side effects
- SCID-X1-IL2 receptor deficiency treated with mouse leukemia virus to transduce stem cells
- apparent cure of 1 case in england and 10 in france
- 4/9 actually got leukemia because the virus inserted next to LMO2 oncogene
17
Q
some viruses cause animal cancers
A
- some naturally occurring animal cancers are infectious and are due to viruses
- breast cancer of mice
- leukemia of domestic cats
- lymphomas of chickens
18
Q
HPV
A
- low risk- 2 and 4 cause warts
- intermediate 11- laryngeal papillomas
- high risk 16 and 18 cause squamous cell carcinoma of cervix, penis, oropharynx
- related to SV 40
- E6 and E7 genes block p 53, E2 suppresses
- progression is slow
- vaccine reduces incidence of CIN
- infection with E6/7 leads to immortalization, co transfection with ras leads to transformation
- need another mutation
- low risk HPVs same thing but low affinity binding
- E2 normally there, lose function when genome integrates-overexpression of 6 and 7
19
Q
E6
A
-binds p53 and leads to degradation of Ub pathway
20
Q
E7
A
- binds non P Rb
- prevents Rb’s interaction with E2F
21
Q
pathogenesis of cervical cancer
A
- CIN I-III- 50% go to cancer
- then get chromosomal instability
- integration at CIN III
22
Q
EBV
A
- mono in western world
- in vitro can transform human B cells with continual expression of some viral genes
- epidemiological evidence links it to human cancers
23
Q
burkitts lymphoma
A
- endemic in african malarian belt
- affects pre pubertal boys
- maxilla most common site
- contains EBV and expresses genes continually
24
Q
nasopharyngeal cancer
A
- endemic in south china, vietnam, arctic eskimos- food related
- contain EBV and express genes continually
- environmental co factors involved
- IgA antibodies to EBV capsid antigen predict tumors or recurrences
25
pathogenesis of EBV related lymphomas
- proliferation
| - translocation Q8-14- gene becomes continually expressed due to Ig heavy chain gene- promoter
26
B cell lymphomas in the western world
- most B cells lymphomas are EBV negative
- in rare cases EBV is present and some genes expressed
- seen in patients with AIDS or long term graft recipients
- may regress if immune function is restored
27
Hep B
- liver cancer incidence is higher in countries with endemic HBV infection
- HBV is a risk factor for cancer
- prospective studies show greater risk with cirrhosis of liver or high level expression of viral genes
- asia and africa
- mechanism of tumors is uncertain but childhood infection is important
- tumor cells contain integrated HBV but no consistent expression of any viral protein in cancer cells
- no activation of cellular oncogene
- virus X gene plus ras can transform cells in culture
28
effect of hep B vaccine
- universal immunization of newborns in taiwan has led to 50% reduction in incidence of HCC in adolescents
- universal immunization of alaskan natives has eliminated HCC
29
human T cell leukemia virus
- 1 in 20 infected people get T cell leukemia after many years
- HTLV1 is integrated into genome of all leukemic cells
- tax expression declines, but HBZ persists
- genetic changes accumulate
- RNA virus with no oncogene
- tax gene causes overexpression of IL2 and its receptor
- other proteins dysregulate RNA metabolism
- blood borne
- prevalent in caribbean countries
30
kaposi's sarcoma virus
- associated with kaposi's sarcoma in patiens with HIV
- DNA virus
- KSHC carrier rate of 50% in Africa
- 10% in eastern europe
- <1% northern europe
- can be latent in B cells
- KS is associated with AIDS in western world
- tumors contain KSHV DNA and express KSVH proteins
31
summary
- retroviruses can cause cancer in animals by transmission of activated oncogenes or by insertional activation of an oncogene
- DNA viruses can cause cancer through effects of T antigen or equivalent, which target p53 and pRb genes
