tumorviruses Flashcards

Question

what is malignant transformation of cells? what are morphogenic characteristics of these cells? (review of biochem last term)

Answer 1

when cells change in growth properties, shape and other features when becoming a tumor cell = altered morphology lose characteristic differentiated shape appear rounded and more retractile under microscope rounding due to disaggregation of actin filaments grow in disorganized, piled-up pattern lose contact inhibition grow in vitro at much lower concentrations of serum than non-malignant cells grow well in suspension - non-malignant cells must be grown adherently can be easily cloned

Answer 2

the cell becomes immortalized - able to continue growing long past the time when when its normal counterpart would have died

Answer 3

tumor viruses can induce DNA synthesis and move cells that were in G1 phase to S phase

Answer 4

the karyotype of infected cells will change - changes in number and shape of chromosomes - deletions, duplications, translocations

Answer 5

virus-encoded proteins preexisting cellular proteins that have been modified previously repressed cellular proteins that are now being synthesized new antigens are recognition sites for immune surveillance against tumor cells

Answer 6

agglutination will be enhanced lectins = plant glycoproteins that bind specifically to certain sugars on the cell membrane surface increased agglutination may be due to clustering of existing receptor sites rather than to the synthesis of new ones

Answer 7

1: reduced levels of cAMP 2: secrete more plasminogen activator 3: increased anaerobic glycolysis => increased lactic acid 4: loss of fibronectin 5: changes in membrane glycoproteins

Answer 8

reduced production | addition of cAMP to malignant cells can cause reversion to non-malignant state

Answer 9

plasminogen activator is a protease that converts plasminogen to plasmin plasmin dissolves the fibrin clot malignant cells secrete more

Answer 10

Warburg effect - cancer cells have increased anaerobic glycolysis and so increased lactic acid production

Answer 11

fibronectin = high molecular weight glycoprotein loss of fibronectin in malignant cells effect of this unknown

Answer 12

changes in the components of glycoproteins and glycolipids in membranes

Answer 13

at least for some viruses to determine this, rous sarcoma virus was made that is temperature sensitive - active at 35 degrees C but not at 39 infect chicken cells at 35, these cells are transformed when incubated to 39, regain normal morphology and behavior return to 35 and go back to transformed morphology therefore, continuous production of some functional virus-encoding protein is required for maintenance of the transformed state

Answer 14

DNA copy of onc gene of chicken retrovirus Rous sarcoma was used as probe DNA in normal embryonic cells hybridized to this probe - indicates that the cells contain a gene homologous to the viral gene

Answer 15

cellular oncogenes but although they're similar, they're not identical cellular have exons and introns viral don't but viral oncogenes likely acquired by incorporation of cellular oncogenes into retroviruses lacking these genes therefore, retroviruses can be thought of as transducing agents

Answer 16

- protein kinases that phosphorylate tyrosine (most protein kinases in cells phosphorylate serine) - cellular growth factors such as EGF - proteins that have effect at cell membrane, such as G-proteins - proteins that act in nucleus by binding to the DNA

Answer 17

growth factor binds receptor on cell membrane membrane g-proteins and tyrosine kinases are activated these interact with cytoplasmic proteins or produce second messengers proteins or second messengers transported to nucleus interact with nuclear factors DNA synthesis activated cell division occurs overproduction or improper expression of any of the proteins in the above sequence can result in malignant transformation

Answer 18

1: DNA-containing cellular oncogenes from tumor cells can transform normal cells in culture - genes have single base change 2: characteristic translocations of chromosomal segments can be seen in certain tumors 3: some tumors have amplification (multiple copies) of some oncogenes - results in overexpression of these genes 4: insertion of the DNA copy of the retroviral RNA (proviral DNA) near a cellular oncogene stimulates expression of c-one gene 5: some cellular oncogenes isolated from normal cells can cause malignant transformation if they have been modified to be over-expressed within the recipient cell

Answer 19

burkitt's lymphoma cells tranlocation moves cellular oncogene c-myc from its normal site on chromosome 8 to a new site adjacent to an immunoglobuilin heavy chain gene on chromosome 14 results in enhanced expression of c-myc

Answer 20

mutation | increased expression

Answer 21

when mutated may not suppress tumor like RB called antioncogenes HPV and SV40 viruses produce proteins that binds to and inactivates RB gene HPV also produces protein that inactivates p53

Answer 22

no. actually, in most cases DNA tumor viruses transform only cells in which they do not replicate all that's necessary for transformation is that one or a few of the viral proteins that are oncogenes are replicated can occur in non-permissive cells

Answer 23

expression of the early genes of the virus | produce set of early proteins called T antogens

Answer 24

proteins produced by early genes of viruses most located in cell nucleus for SV40 gene, large T antigen is necessary and sufficient for tumorigenesis has protein kinase and ATP activity mostly located in nucleus, but some in outer cell membrane where can be detected by transplantation antigen tumor specific transplantation antigen (TSTA)

Answer 25

RNA tumor viruses affect proto-oncogenes by introducing, up-regulating or mutating them - affect on the DNA of the host cell - since acting on genes, is somewhat heritable DNA viruses act on tumor suppressor genes by inactivating them - act at the protein level - sequester or degrade them

Answer 26

1: by inserting an oncogene into the host geneome - only happens in transducing retroviruses - no known human examples known 2: by random insertion into the host genome by altering expression of an existing cellular oncogene - only in non-transducing retroviruses 3: by altering growth properties of cells, rendering them more likely to enter a transformed state - done by non-transducing long latency retroviruses and DNA tumor viruses such as EBV and HHV-8 4: by infecting cells and altering activity/stability of cell cycle-related proteins with or without an integration effect - seen in DNA tumor viruses such as papilloma virus and hepadnaviruses such as hep b may fall into this category 5: other mechanisms in vivo, such as chronic tissue damage that causes regeneration of tissue - such as what hep C does in the liver hep B may also fall in to this category

Answer 27

+stranded RNA viruses but must go through a DNA intermediate to make mRNA this DNA integrates into the host cell genome while some other viruses make DNA, retroviruses are the only ones for which integration into the genome is essential for replication and that can get out - only ones where integration is a viable concern

Answer 28

two identical strands of +sense RNA

Answer 29

reverse transcriptase integrase - integrates DNA into host genome protease

Answer 30

transducing non-transducing non-transducing, long latency

Answer 31

usually need coinfection with another virus to get integration of genome - lost one of their growth genes and acquired a cellular oncogene insert their oncogene into the host DNA

Answer 32

almost 100% of infected cells will get tumors | tumor latency matter of days

Answer 33

slow tumor latency have not acquired a snark insert into the wrong spot in genome - cause endogenous genes to be mistranslated LTR gets inserted - it's a downstream enhancer - orientation independent so can insert anywhere in genome and can act on genes far away as enhancers or can act as promoters to adjacent genes

Answer 34

viral DNA has LDRs on the side - strong promoters of transcription - where they insert into the genome, will induce high transcription rates for viral DNA RNA that's made and part of genome gets deleted - acquires piece of host DNA downstream from that deletion spot - if it was an oncogene, virus now carries oncogene can also occur if virus just also replicates snark gene and so has an additional oncogene component

Answer 35

since the end sequence that was replaced by an oncogene is no longer there, the viral DNA can't get out of the host DNA so can't replicate unless there's a helper virus also in the cell that contains the end-gene needed to get the DNA out of the genome

Answer 36

we have two copies of these genes, so even if one is suppressed, it's very unlikely that the virus would also suppress the other and so the gene will still be expressed

Answer 37

could be used for gene therapy to insert a correct gene into the genome of those who have mutated versions recently used to reverse SCID, but trial was halted due to the development of leukemia in 3 kids

Answer 38

20 million worldwide

Answer 39

no clinical manifestations but 2% of female carriers and 6% of male carriers develop adult T cell lymphoma/leukemia

Answer 40

greater than 30 years often

Answer 41

usually lifelong, but there's no clinical manifestations

Answer 42

sexually and via IV drug use or transfusion

Answer 43

even though the tumor cells are clonal for insertion, there doesn't seem to be any chromosomal location specificity

Answer 44

``` gag pol env LTRs (Long Terminal Repeats are not actually genes. They are structural elements in the viral genome that allow for the insertion of functional genes into the host genome.) and Tax ```

Answer 45

carried in HTLV transcription factor tax --> NF(kappa)B --> IL-2 --> proliferation

Answer 46

tax leads to increase in IL-2, which leads to increase in T-cell proliferation this rapid rate of proliferation leads to t cell malignancy

Answer 47

the virus will insert at the same insertion site in all of the cells from the same person

Answer 48

prostate cancer - seen in 27% of prostate cancers | also found in blood of CFS patients

Answer 49

it's unclear as to what group it belongs in could be non-transducing or long latency has no known oncogene

Answer 50

- interfere/inactivate tumor suppressors - p53 and RB are common targets - stimulate/interfere with cell signaling - produce cyclin homologs - inhibit apoptosis - inhibit immune response to tumors

Answer 51

it produces the LT protein, which sequesters p53

Answer 52

antivirals and vaccines imiquimod (aldara) is a topical cream potent agonist of TLR7 and IFNalpha see resolution of lesions from 0-5 months

Answer 53

in various animals but there's no evidence that it causes cancer in humans

Answer 54

Jaw, abdominal, and also in the heart

Answer 55

subsaharan/equatorial africa

Answer 56

with highest rates of HIV and malaria

Answer 57

increases size and activity of germinal centers these germinal centers are the sites of somatic mutation of Ig regions for maturation of Ab responses LMP-1 protein drives B cells to proliferate - enters germinal centers greater than 90% of cases of burkitt's lymphoma have a reciprocal translocation that results in the movement of the proto-oncogene c-myc from chromosome 8 to the proximity of the antibody genes on chromosome 14 => overexpression of c-myc => transformation and cancer

Answer 58

exogenous cytokines

Answer 59

cofactors from HIV/immunosuppression

Answer 60

it's highly angiogenic, so increases blood supply to tumors | viral IL-6 and v-GPCR homologs are essential for tumor growth - these cause cells to replicate

Answer 61

hep B and C

Answer 62

has an x protein that seems to target p53 and fos-myc DNA may integrate into genome causes chronic inflammation

Answer 63

likely through chronic inflammation non-cytolytic does not have DNA intermediate, oncogene, or DNA integration