M2-C3-L81 --> Rna Tumor Virology

Front 1

How does RNA tumor viruses "create" oncogenes?

Back 1

By acquiring, modifying and deregulating cellular genes (proto-oncogenes)

Front 2

For RNA tumor viruses, are viral oncogenes essential viral genes?

Back 2

NOT essential

Front 3

For RNA tumor viruses are viral oncogenes related to its strategy of viral replication?

Back 3

NOT related

Front 4

T/F - Replication of RNA virus is cytocidal.

Back 4

False

Front 5

T/F - Replication of RNA virus is required for tumorigenesis.

Back 5

False

Front 6

Once the RNA tumor virus integrates into DNA host chromosome, expression of the provirus is under control of what?

Back 6

LTRs

(viral transcription regulatory sequences)

Front 7

What are the mechanisms of cell transformation for RNA tumor viruses? x3

Back 7

Retroviral TRANSDUCTION of oncogene

Activation of oncogene by retroviral INSERTION.
(cis-acting)

Mediation of oncogenesis by essential retrovirus PROTEINS
(trans-acting)

Front 8

Transducing retrovirus:

- has capacity to do what?
- options x2 with v-onc?
- why does it need helper virus?

Back 8

Transform if deregulated

Overexpression of it
Change its structure

B/c secondary loss of viral coding info has made it replication defective

Front 9

For RNA tumor viruses, acquired genes are components of what?

Back 9

signaling networks

Front 10

What are the components of the signaling network that is acquired by the RNA tumor virus?

Name components for each.

Back 10

External signal molecules
(sis)

Cellular receptor
(erbB, fms, kit)

Secondary messengers in signaling cascade
(kinases: src, abl, yes, fgr, mos raf)

Transcription factors
(myb, myc, jun, rel, fos, ets)

Front 11

RNA tumor virus will structurally change the Epidermal Growth Factor Receptor (EGFR or cErb B) into what? how?

How does this altered receptor function?

Back 11

v-Erb B

Transduced viral gag on it

Constitutively activated receptor

Front 12

Retroviral Transduction outcome x3

Back 12

"Single hit" carcinogenesis

Tumors in days

Polyclonal
(tumor growth initiated in every cell)

Front 13

RNA tumor virus Retroviral Transduction is characteristic of what kind of viruses?

Back 13

ANIMAL retroviruses.

Front 14

Activation of oncogenes by retroviral insertion:

- random?
- activation by how?
- insertion where?

Back 14

Yes

cis activation by promoter/enhancer

insertion next to proto-oncogenes (encoded by exons 1-3)

Front 15

Cis-acting oncogenes:

- carry what oncogenes
- retain what viral genes
- replicate?

Back 15

NO oncogenes

ALL viral genes

Replication competent

Front 16

Outcome of oncogene activation by retrovirus insertion? x3

Back 16

1. Slow-induced (months) tumors

2. Transformation of cell (RARE)

3. Monoclonal tumors

Front 17

Why are cell transformations rare when oncogene is activated by retrovirus insertion.

Back 17

Because the probability of insertion near a potential oncogene is RARE.

Front 18

Why are tumors derived from the outcome of oncogene activation by retrovirus INSERTION, so slow (months)?

Back 18

B/c tumor derived form single cell.

Front 19

In gene therapy, a retroviral insertion near what gene can cause childhood T-cell leukemia.

What does this do?

How does this cause CA?

Back 19

LMO2

Blocks T-cell differentiation

The subsequent insertion of IL-2Receptor (absent in SCID) causes massive cell division.

Front 20

HTLV-1 is type A B or C

Back 20

C

(thus no precursor, central core)

Front 21

T/F - HTLV-1 carries cellular oncogenes.

Back 21

False

Just like cis.

Front 22

Adult T-cell Leukemia (ATL) has what symptoms?

Back 22

Skin nodules all over

Front 23

HTLV-1:

- envelope?
- central core components? x3

Back 23

Yes

Structural proteins
2 copies of RNA genome
Enzymes (RTase, protease, integrase)

Front 24

HTLV-1 Transmission routes: x3

Back 24

Sexual (mostly male to female)

Vertical

Blood products

Front 25

For successful transmission of HTLV-1 what must happen cellularly? via?

Back 25

Cell-to-cell contact transmission

MTOC - with GAG, ICAM, LFAT, Tax

Front 26

T/F - Cell-free HTLV1 is NONinfectious.

Back 26

True

Front 27

How do you screen for HTLV-1 in donated blood?

Back 27

ELISA and Western blot

Front 28

Seroprevalence of HTLV is greater or lesser than HIV?

Which serotype of HTLV is most common and seen in what population group?

What is the oncogenic potential of this?

Back 28

Greater 3x

HTLV-2

IV drug users

NO oncogenic potential

Front 29

Two major diseases associated with HTLV-1.

Back 29

ATL

HAM (HTLV-1 Associated Myelopathy)

Front 30

HTLV1 infects what cells?

Back 30

CD4+ T cells

Front 31

ATL:

- onset when
- diagnosis test
- does chemo help?

Back 31

20-40 years after primary infection

Antibody detection of CD4 and CD25

Minimal improvement of survival

Front 32

ATL:

- what are the two types and describe

Back 32

Fulminant (survival 6 mos)

Indolent (50% 4 year survival)

Front 33

Pathologic diseases associated with ATL. x3

Back 33

Lymphadenopathy
Hepatosplenomegaly
Skin involvement

Front 34

Lab tests with ATL would show what? x2

Why?

Back 34

Elevated Serum calcium levels

Lytic bone lesions

(overexpression of PTH-related protein)

Front 35

HTLV:

- what are the regulatory gene products responsible for pathogenesis? x2

- what ar the regulatory proteins responsible for replication and gene expression?

Back 35

Tax and HBZ

Tax and Rev

Front 36

HTLV-1 has HBZ encoded from which part of genome?

Back 36

MINUS strand of provirus

Front 37

Tax:

- regulates expression of
- binds what? why?
- dissociates
- upregulates what?

Back 37

viral genes

Transcription factors to enhance their binding to cellular PROMOTERS.

NF-kB/IkB complexes

IL-2, IL-2R alpha, IL-1, IL-3,.....

Front 38

Tax targets cell cycle regulatory proteins (like DNA) how? x2

Back 38

Inactivates p53

Binds MAD1 (interfering with G2/M phase)

Front 39

ATL has Atypical "flower cells"

- reflects what?
- found where?
- what are these?
- describe its nuclei x2

Back 39

Tax expression
(elevated levels of IL-2R)
(perturbed chr segregation - MAD1)

CSF and Blood

Wierd CD4+ T cells

Indented, convoluted

Front 40

Is Tax continuously expressed in the tumor itself?

Why or why not?

Back 40

No. simmers down its expression

To avoid antibody detection

Front 41

How do T-cells proliferate without Tax protein expression?

Back 41

HBZ protein influences host gene expression (AP1 transcription) to drive replication.

mRNA that has just encoded for HBZ protein will go off and drive proliferation of T-cells via the E2F1 pathway.

Front 42

What are the bimodal protein functions for HBZ

Back 42

Influence host gene expression for T-cell proliferation
(via AP1 transcription)

Suprress transcription of viral genes (Tax encoding genes) from the plus trand.

Keep in mind that Tax came from MINUS strand.

Front 43

HTLV-1 Induced Oncogenesis:

- type of process
- latency duration

Back 43

Multistep process
(not just caused by virus, but other factors)

LONG -> Decades

Front 44

HTLV-1:

Is Tax expressed in tumors?

Back 44

Although involved in tumor initiation,

OFTEN NOT expressed

Front 45

What type of tumors do you get with HTLV-1?

Back 45

Monoclonal

BUT integration site VARIES among patients.
(NO cis-activation)

Front 46

T/F - Tax is a STRUCTURAL protein.

Back 46

False

It is NON structural

Front 47

T/F - In maintenance of ATL transformation, HBZ and Tax are both expressed.

Back 47

False

Only HBZ

Front 48

Questions Ho

Back 48

Answers Biatch