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VET 413: Infectious Disease/Immunology > Retroviruses > Flashcards

Retroviruses Flashcards

1
Q

what is the goal of viruses

A

to replicate and persist through time

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2
Q

what is unique about retrovirus replication

A

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

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3
Q

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

A

reverse transcriptase

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4
Q

what is the basic, 4 component genome structure of retroviruses

A

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

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5
Q

LTR

A

flanking long terminal repeats

contain viral promoter, enhancer, termination, and polyadenylation sites

enhancer: recruits transcription factors
promoter: facilitates binding of TFs

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6
Q

gag

A

group specific antigen

encodes core structural proteins

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7
Q

pol

A

polymerase

encodes reverse transcriptase, integrase, protease, and endonuclease

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8
Q

env

A

envelope

encodes membrane glycoproteins, viral attachment protein, and fusion protein

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9
Q

steps of retrovirus replication

A
  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
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10
Q

steps of gag formation

A
  1. mRNA gets exported out of nucleus and into cytoplasm
  2. translated into gag core structural proteins
  3. transported to cell membrane
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11
Q

steps of env formation

A
  1. mRNA gets exported out of nucleus and to the ER
  2. translated into env membrane proteins
  3. transported to cell membrane
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12
Q

steps of viral genome formation

A
  1. mRNA gets transported out of the nucleus and into the cytoplasm
  2. two copies of mRNA get transported together to the cell membrane
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13
Q

provirus

A

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

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14
Q

virion

A

new virus that gets released from the host cell

contains two copies of the + sense ssRNA genome

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15
Q

exogenous retroviruses

A

horizontally transmitted virus that undergoes normal viral replication

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16
Q

endogenous retroviruses

A

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

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17
Q

are endogenous viruses able to replicate

A

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

18
Q

can viruses have both an endogenous and exogenous form

A

yes - 6 retroviruses have both

most exogenous viruses occur without endogenization but some do get endogenization

19
Q

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

A

can restrict or promote infection with exogenous virus

20
Q

what is a clinical consideration of retrovirus infections

A

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

21
Q

what are retroviruses classified based on

A

nucleotide sequence
pathophysiology

22
Q

pathophysiology of retroviruses

A
  1. acute –> rapidly transforming
  2. chronic –> slowly transforming
  3. immunosuppressive
23
Q

nucleotide sequence of retroviruses

A

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

spumaretrovirinae: spumaviruses

24
Q

what are the main alpha retroviruses

A

ALV, RSV

affects chickens
tumor producing

25
Q

what are the main beta retroviruses

A

JSRV, ENTV

affects sheep, goats
tumor producing

26
Q

what is the main gamma retrovirus

A

FeLV

affects cats
tumor producing

27
Q

what is the main delta retrovirus

A

BLV

affects cows
tumor producing

28
Q

what are the main lentiviruses

A

SRLV, FIV, EIA

affects sheep/goats, cats, horses (respectively)
immunosuppressive

29
Q

what are the mechanisms of retrovirus oncogenesis

A
  1. insertional mutagenesis
  2. oncogene capture
  3. oncogenic viral protein
30
Q

tumor suppressor genes (TSGs)

A

suppresses/slows down the cell cycle

Rb and p53

31
Q

proto-oncogenes

A

signals for the cell cycle to continue

32
Q

insertional mutagenesis

A

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

33
Q

cis-activation vs trans-activation

A

cis: activation of a nearby host gene

trans: activation of a distant host gene

34
Q

effect of endogenous murine leukemia virus on exogenous infection

A

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

35
Q

oncogene capture

A

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

36
Q

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

A

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

37
Q

proto-oncogene

A

comes from the host cell genome

ex. C-src

38
Q

oncogene

A

transcribed version of the proto-oncogene once integrated into viral genome

ex. V-src

39
Q

oncogenic viral protein

A

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

40
Q

tax

A

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

VET 413: Infectious Disease/Immunology (38 decks)

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