Viruses and Cancer

Question 1

Rous Sarcoma Virus

Answer 1

caused cancer when given back to a chicken

had etra “src” gene accidentally stolen from host cell - not required for virus multiplication but for transformation

Question 2

v-src

Answer 2

Rous Sarcoma, captured c-src

c-src is normal cell gene that regulates proliferation (protooncogene)

protein tyrosine kinase

virus doesnt use

always on in host cell - mutated captured host in the mutated form!

how we learned about proto-oncogenes

Question 3

c-onc

Answer 3

protooncogenes

generally encode proteins that reg cell growth or differentation

v-onc is usually mutant, constitutively active proteins expressed at high levels

viruses kidnapped mutated proto-onc genes

dominant GOF –> uncontrolled proliferation

Question 4

HTLV-1

Answer 4

adult T cell leuemia

no proto-oncogenes

Tax - growth promotion –> transcriptional canges –> ATL, aneuploidy T cells)

cells usually don’t have Tax bc CTLs kill cells that express Tax

Question 5

HBZ

Answer 5

protein that suppresses proliferation so adult t cell leukemia doesn’t lead to ATL (latent period)

Question 6

TAX

Answer 6

protein that stimulates growth in T cells

in HTLV-1 virus

turn on Akt and NFkB for cell growth and cell survival

Question 7

papovavirus

Answer 7

papilloma

polyomavirus

vaculating virus

small DNA tumor virus

stable

Question 8

DNATV genome

Answer 8

small dsDNA genome

non-enveloped

replication initiator

stimulates proliferation (transformation)

REQUIRE host DNA replication proteins (DNA-dep DNA pol)

must advance quiescent cells into S phase

Question 9

papillomaviruses

Answer 9

dsDNA

host and tissue specific

virus is sparse in most lesions

Question 10

stratified squamous epithelia and HPV infection

Answer 10

basal layer replicates

move up layers and differentiates - lose ability to divide

virus infects basal layer and induces cell proliferation (viral genome maintained and segregated)

continue to divide as cells differentiate

infections virus is only made in outermost layer

Question 11

CIN formation

Answer 11

from varying degrees of HPV induced proliferation in stratified squamous epithelia

test with pap smear

most individuals resolve

some progress to in situ carcinoma (invasive)

Question 12

CIN1

Answer 12

very mild dysplasia

Question 13

CIN2

Answer 13

moderate dysplasia

Question 14

CIN3

Answer 14

severe dysplasia

in situ carcinoma

Question 15

SCCA

Answer 15

invasive carcinoma

Question 16

SIL

Answer 16

squamous intraepithelial lesion

low grade - CIN 1

high grade - CIN 2, CIN 3

Question 17

VLPs

Answer 17

HPV vaccine!

virus like particles

take L1 gene from virus DNA and paste into another microbe

make L1 - self assemble - empty protein shell without DNA

looks like HPV virus

Question 18

HPV DNA integration

Answer 18

no consequence or cervical cancer

dead end for virus!

loss of p53 (genomic instability)

interrupt E2 - can’t regulate cell replication (high E6, E7)

Question 19

E6, E7

Answer 19

stimulate cellular proliferation

needed for productive viral growht

when genome is integrated, fuel cancer cell proliferation

Question 20

Rb and HPV

Answer 20

tumor suppressor gene

cell cycle regulator - inactive when P (late G1), active when noP (quiescent - early G1)

unP - binds and inactivates E2F - no DNA replication!

E7 binds Rb –> releae E2F –> make cellular/viral replication proteins!

Question 21

HPV and p53

Answer 21

tumor suppressor - at G1 phase

activates transcription of genes that arrest cell cycle and can promote apoptosis

E6 - binds p53 and sends it to proteasome to be degraded - cell can divide!

Question 22

BK

Answer 22

early childhood - mild respiratory

lifetime persistance

immortalizes animal cells

tumorogenic in newborn animals

Question 23

JC

Answer 23

isolated from immunosuppressed patient with demylinating disease PML

Question 24

Merkel Cell Plyomavirus

Answer 24

merkel cell carcinoma - rare, aggressive skin cancer in elderly and immunosuppressed

found in a clonal form integrated

first integrated PyV with malignancy