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MSII Micro Unit 1 > Oncogenic Viruses > Flashcards

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
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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
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3
Q

myc

A

-TF

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4
Q

src

A

-membrane signaling of GF binding

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5
Q

ras

A

-signal transduction from surface receptors

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6
Q

sis

A

-platelet derived GF

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7
Q

erb B

A

GF receptor

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8
Q

fms

A

GF receptor

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9
Q

LMO2

A

hematopoiesis

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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
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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
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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
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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
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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.

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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
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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
Q

pathogenesis of EBV related lymphomas

A
  • proliferation

- translocation Q8-14- gene becomes continually expressed due to Ig heavy chain gene- promoter

26
Q

B cell lymphomas in the western world

A
  • 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
Q

Hep B

A
  • 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
Q

effect of hep B vaccine

A
  • 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
Q

human T cell leukemia virus

A
  • 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
Q

kaposi’s sarcoma virus

A
  • 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
Q

summary

A
  • 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

MSII Micro Unit 1 (5 decks)

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