Retroviruses

Question 1

what is the goal of viruses

Answer 1

to replicate and persist through time

Question 2

what is unique about retrovirus replication

Answer 2

violates central dogma - begins with an RNA genome and must convert to DNA
- DNA can be used to create new viral genome or code for viral proteins

vRNA –> DNA –> vRNA
AND
vRNA –> DNA –> mRNA –> protein

Question 3

what enzyme is required for viruses to be able to go from RNA to DNA

Answer 3

reverse transcriptase

Question 4

what is the basic, 4 component genome structure of retroviruses

Answer 4

5’ methyl cap
LTR
gag
pol
env
LTR
3’ polyA tail

Question 5

LTR

Answer 5

flanking long terminal repeats

contain viral promoter, enhancer, termination, and polyadenylation sites

enhancer: recruits transcription factors
promoter: facilitates binding of TFs

Question 6

gag

Answer 6

group specific antigen

encodes core structural proteins

Question 7

pol

Answer 7

polymerase

encodes reverse transcriptase, integrase, protease, and endonuclease

Question 8

env

Answer 8

envelope

encodes membrane glycoproteins, viral attachment protein, and fusion protein

Question 9

steps of retrovirus replication

Answer 9

1. envelope proteins bind to host cell receptors
2. fusion, entry, and uncoating of virus into cytoplasm of host cell
3. reverse transcription of vRNA –> dsDNA by reverse transcriptase in the cytoplasm
4. DNA translocates to nucleus –> integrates into host cell genome to form a provirus
5. host cell begins replicating –> provirus gets transcribed into mRNA
6. mRNA copies become one of the three: gag, env, viral genome
7. all three components transport to cell membrane and get packaged/assembled to form a new virus
8. virion blebs off of the cell membrane surrounded by env surface proteins

Question 10

steps of gag formation

Answer 10

1. mRNA gets exported out of nucleus and into cytoplasm
2. translated into gag core structural proteins
3. transported to cell membrane

Question 11

steps of env formation

Answer 11

1. mRNA gets exported out of nucleus and to the ER
2. translated into env membrane proteins
3. transported to cell membrane

Question 12

steps of viral genome formation

Answer 12

1. mRNA gets transported out of the nucleus and into the cytoplasm
2. two copies of mRNA get transported together to the cell membrane

Question 13

provirus

Answer 13

form of the virus that is integrated into the host cell genome

Question 14

virion

Answer 14

new virus that gets released from the host cell

contains two copies of the + sense ssRNA genome

Question 15

exogenous retroviruses

Answer 15

horizontally transmitted virus that undergoes normal viral replication

Question 16

endogenous retroviruses

Answer 16

vertically transmitted virus that becomes permanently integrates into the host cell genome

infects the germline (egg/sperm) –> all cells of that offspring will have virus incorporated into genome –> acquires mutations as it continues to be passed in germline

virus gets recognized as “self” - animal does not generate an immune response

Question 17

are endogenous viruses able to replicate

Answer 17

most are NOT able to replicate and are “inert” fossils in the DNA

Question 18

can viruses have both an endogenous and exogenous form

Answer 18

yes - 6 retroviruses have both

most exogenous viruses occur without endogenization but some do get endogenization

Question 19

how does the presence of an endogenous virus affect the ability of the exogenous form to infect host

Answer 19

can restrict or promote infection with exogenous virus

Question 20

what is a clinical consideration of retrovirus infections

Answer 20

gets integrated into host cell genome - causes PERSISTENT infections

“infected for life” but not always detected on PCR because not viremic once integrated into genome

Question 21

what are retroviruses classified based on

Answer 21

nucleotide sequence
pathophysiology

Question 22

pathophysiology of retroviruses

Answer 22

1. acute –> rapidly transforming
2. chronic –> slowly transforming
3. immunosuppressive

Question 23

nucleotide sequence of retroviruses

Answer 23

orthoretrovirinae: a, B, y, d, e virsues + lentiviruses

spumaretrovirinae: spumaviruses

Question 24

what are the main alpha retroviruses

Answer 24

ALV, RSV

affects chickens
tumor producing

Question 25

what are the main beta retroviruses

Answer 25

JSRV, ENTV affects sheep, goats tumor producing

Question 26

what is the main gamma retrovirus

Answer 26

FeLV affects cats tumor producing

Question 27

what is the main delta retrovirus

Answer 27

BLV affects cows tumor producing

Question 28

what are the main lentiviruses

Answer 28

SRLV, FIV, EIA affects sheep/goats, cats, horses (respectively) immunosuppressive

Question 29

what are the mechanisms of retrovirus oncogenesis

Answer 29

1. insertional mutagenesis 2. oncogene capture 3. oncogenic viral protein

Question 30

tumor suppressor genes (TSGs)

Answer 30

suppresses/slows down the cell cycle Rb and p53

Question 31

proto-oncogenes

Answer 31

signals for the cell cycle to continue

Question 32

insertional mutagenesis

Answer 32

integration of the retrovirus in the genome: 1. within a TSG: causes TSG dysfunction --> unable to suppress cell cycle 2. near a porto-oncogene promoter: creates powerful promoter (LTR) --> cis-activation of proto-oncogene --> rapid recruitment of host cell machinery --> rapid cell division causes unregulated, rapid cell division --> tumor formation

Question 33

cis-activation vs trans-activation

Answer 33

cis: activation of a nearby host gene trans: activation of a distant host gene

Question 34

effect of endogenous murine leukemia virus on exogenous infection

Answer 34

endogenous MLV is protective against exogenous MLV infection by increasing transcription of antiretroviral restriction factors that limit the ability of MLV to infect host cells

Question 35

oncogene capture

Answer 35

retrovirus co-opts proto-oncogenes from the host cells and integrates it into their own viral genome often LACKS regulatory elements --> allows them to replicate unregulated

Question 36

are retroviruses that use oncogene capture able to replicate on their own

Answer 36

most are NOT able to replicate - require a helper virus integration of proto-oncogene into genome causes loss of part of their own genome exception: RSV - able to conserve viral genome

Question 37

proto-oncogene

Answer 37

comes from the host cell genome ex. C-src

Question 38

oncogene

Answer 38

transcribed version of the proto-oncogene once integrated into viral genome ex. V-src

Question 39

oncogenic viral protein

Answer 39

retrovirus directly encodes the oncogenic viral protein via one of two mechanisms: 1. virus has an additional oncogene segment in its genome (ex. BLV) 2. virus encodes oncogenic proteins directly though their env protiein

Question 40

tax

Answer 40

potent transcriptional activator that promotes production and transcription of viral genome via positive feedback and able to activate other host genes via trans-activation