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45 Cards in this Set

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List the human DNA tumor viruses of the:

- polyomaviruses x3
- herpesviruses x2
- hepadnoviruses x1
BK virus
JC virus
SV-40 virus

EBV
KSHV

Hepatitis B virus
List the human RNA tumor viruses of the:

- retroviruses x1
- flavivirus x1
HTLV-1

Hepatitius C virus
Cellular oncogenes are deregulated by what? x2
Overexpression

Mutation
Viral oncogenes defined.
Virus-acquired cellular proto-oncogenes.
Loss of function for what gene leads to CA?
Tumor suppressor gene
Effects on cellular genes:

- RNA tumor viruses
- DNA tumor viruses
Activates proto-oncogenes

Negates cellular TUMOR SUPPRESSOR GENE
What is the primary function of proto-oncogenes?
Signal transduction from cell surface to the nucleus.

(also has growth stimulation potential)
DNA tumor viruses target what two pathway altering proteins?
Rb (Retinoblastoma protein)

p53
DNA vs RNA tumor viruses oncogenes:

- v-onc enssential?
- cellular homologue?
- affects signaling pathway how?
- association with strategy for viral replication
DNA: essential viral genes
RNA: NOT essential viral genes

DNA: NO cellular homologue
(v-onc not cellularly obtained)
RNA: acquired cellular genes

DNA: INACTIVATE tumor suppressors
RNA: DEREGULATE signal pathway

DNA: linked
RNA: unrelated
What type of target cell does DNA tumor virus like to undergo transformation?
Quiescent
Differentiated
Non-conducive to viral replication
Viral oncogenes encoded by ______ preparing the cell for?
Early genes

Viral replication
DNA tumor virus transformation will inhibit what 2 tumor suppressor proteins that prevent what progression?
Rb and p53

G1 progression
List the three small DNA tumor viruses.
HPV

SV40

Adenovirus
For DNA tumor viruses, transformation only occurs when?

what happens here?
in the "aborted" viral life cycle

Early genes expressed
Replication (which is cytocidal) does not occur
Adenovirus:

- gene product
- cellular target
E1A -> Rb
E1B -> p53
SV 40:

- gene product
- cellular target
Large T antigen -> Rb
Polyomavirus

- gene product
- cellular target
Large T antigen -> Rb

Middle T antigen -> Src and PI3K
Papillomavirus

- gene product
- cellular target
E7 -> Rb
E6 -> p53
E5 -> PDGR Receptors
What would you seen in CIN I for a HPV infection? x4
Differentiated Cells
Infectious virus
Koilocytes
Episomes
What would you seen in CIN III for a HPV infections? x4
Undifferentiated Cells AT ALL LAYERS
Integrated virus DNA
Cancer
High Dysplasia
For HPV, an E2 disruption upon integration would lead to what event?
Loss of regulation for E6 and E7
During HPV integration what oncogenes are preserved? x3
E6
E7
LCR (long control region)
During HPV integration what oncogenes are lost? x2
E2

Other genes needed to replicate virus are lost
What are the outcomes of small DNA tumor virus infection? x3
Cell cycle deregulation
(no consequence if cell dies secondary replicative infection)

Monoclonal tumors
(same viral DNA integration site in all cells)

Transformation (rare, but possible in non-permissible cells)
Transformation requires what? x2
Abortive infection

Integration of intact viral gene
EBV LMP1 mimics what?

E5 gene of bovine papillomavirus mimics what?
CD40 receptor

PDGF Receptor
HHV-8:

- # of strands in genome
- linear or circular genome
- what subfamily?
double stranded

Linear, but circular once inside cell

Gammaherpesvirus
HHV-8 (or KSHV)

- Ubiquitous?
- Strong risk factor?
- #1 Reservoir
NOT ubiquitous
(very uncommon)

AIDS

B-cells
Kaposi's sarcoma:

- clinical symptoms
- driven by what process
Multiple vascular nodules of skin, mucous membrane, and viscera

Cytokine
Kaposi's sarcoma:

- What would you expect to see on a histological slide? x4
Proliferation of Spindle/Endothelial cells

Infiltrating inflammatory cells

Extravasation of erythrocytes

Extensive Neoangiogenesis
Kaposi's sarcoma:

- transmission x2
- endemic where?
- epidemic where?
- classic KS?
sexual
saliva

Central Africa
(younger age, more women, aggressive)

AIDS patients (homos)

Older Mediterranean men
(benign, distal extremities)
Detection of HHV-8 in all histological views show what forms?

What does this indicate?
Identical

Common etiology
T/F - Kaposi's is only longitudinal transmission.
False.

Can be vertical also.
What tests would detect HHV8 and get samples from where? x4
PCR

saliva
semen
prostate
peripheral blood lymphs
HHV8 "pirates" cellular genes that regulate what? x3
Angiogenesis

Cell cycle

Inflammation
List three diseases associated with HHV8.
Kaposi's Sarcoma

Body cavity-based primary effusion lymphomas

Multicentric Castlemen's Disease
Body cavity-based primary effusion lymphomas:

- describe mass
- what molecules are not expressed
- often co-infected with what other virus?
Non-contiguous mass

Adhesion molecules

EBV
Multicentric Castlemen's Disease

- describe mass
- location
- what cellular process involved?
Non-neoplastic lymphoproliferation

Generalized or as solitary mediastinal node

IL-6 overexpression (viral or cellular)
viral IL-6 expression is relevant in the pathogenesis of what two diseases?
Kaposi's and Castlemans
List the HHV-8 pirated cellular proto-oncogenes and describe what they do? x5
1. viral Bcl-2 (APOPTOSIS regulator)

2. viral IL-6 (ANTI-APOPTOSIS, B-Cell growth stimulator)

3. viral G-Protein coupled receptor (ANGIOGENIC activity)

4. viral IFN regulatory factor (negative regulator of INF signaling)

5. viral Cyclin (Cell Cycle regulator)
Which are the lytic cellular proto-oncogenes that are pirated by HHV-8?
Bcl-2

IL-6

G-protein-coupled receptor
KS is the most common malignancy associated with what other disease?
AIDS
What has dropped the incidence of KS by 50-75%?
HAART
T/F - KSHV Genome encodes genes that are homologous to cell-signaling and regulatory pathway proteins.

If this were true, what is this called?
TRUE

Molecular mimicry
KSHV is a DNA tumor virus with oncogenes acquired from what genes?
Cellular