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Immunology 3 > #6 Retrovirus I > Flashcards

#6 Retrovirus I Flashcards

1
Q

Infection consequences:

A
  • no ill effects, tumors (rapid onset or long latency), wasting disease (neurodisorders), immune deficiences (HIV)
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2
Q

REtroviruses affects on host chromosomes or cell sequences

A

Aquire host cells sequences—oncogenes

Insert into host cells chromosomes—can actiate or inactivate genes > > cancer

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3
Q

Classification; based on

A

pathogenicity or shape but not relfect evolutionary relationships observed by sequence comparisons

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4
Q

MOre on classification system, how may groups

A

Either complex or simple and there is a total of 7 dif groups
based on genome structure and how many proteins they encode

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5
Q

retrovirus: Enveloped virus, env protein embedded in membrane, ________ under lipid bilayer

A

matrix protein

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6
Q

Capsid (core) made up of structual proteins called

A

(group of specific antigens or products of the ‘gag’ genes)

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7
Q

Gag genes

MA.CA.NC.PR

A

Matrix, Capsid, NucleoCapsid, Protease

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8
Q

what is unique about retrovirus genome

A

2 copies of (+) ssRNA genome.

Only virus is ‘diploid’ and accounts for recombiantion potential

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9
Q

TM and SU are made as GP______ or one protein that gets clipped

A

160

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10
Q

Retroviral genomic RNA is made by hosts Pol II so they are _______and _______ like other host Poll mRNAs

A

capped and polyadenylated

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11
Q

Capped Ends

a. R at start and end; it’s a ‘_____’ sequence and is at both ends

A

repeat

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12
Q

U5 is at the_____

U3 is at the_____

A

start

end

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13
Q

Gag gene: MA/CA/NC/PR are made as a

A

polyprotein that then gets clipped

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14
Q

-in HIV, the _____is in “pol” gene reading frame

A

PR

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15
Q

Pol Gene: polymerase gene has

A

RT

IN

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16
Q

RT-
IN-
together they =

A

reverse transcriptase
integrase
together = extended polyprotein

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17
Q

Envelope (env) gene: encodes env protein, made as precursor HIV, gp of 160→

A

to gp of 120 + 41

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18
Q

Complex Retrovirus organization

simular to simple (w/ gag-pol-env) but

A

more additional genes/proteins

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19
Q

Complex Retrovirus has mRNAs for

A

additional genes, the ‘accessory proteins’ are generated by complex splicing (simple retrovirus do a single splice to make env)

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20
Q

How does a complex retrovirus generate ‘accessory proteins’

A

using the mRNA for complex alternative splicing

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21
Q

Difference in splicing for simple vs complex retrovirus

A

simple splice once

complex splic multiple times

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22
Q

how many classes of RNA are derived form extensive splicing

A

3 classes

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23
Q

replication cycle sepearted into two phases by integration step:
1st phase steps A-E will ______ integration and 2nd phase (F-J) is_____ ingration

A

precede

post

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24
Q

1st step:

Absorption

A
  1. Virus binds cell via env protein and host cell receptor
  2. HIV receptor is CD4/CCR5 (specifics for T cells)
  3. other viruses use aa transporters, LDL- like receptor, many others
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25
Q

During absorption, the virus binds to the cell via the _____ protein

A

env

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26
Q

HIV receptor for absorption is ________

other retros us ______

A

CD4 or CCR5 (makes them T cell specific)

aa or LDL like receptors

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27
Q

2nd step: Penetration/uncoating

two main steps

A

viral envelope fuses with cell membrane at surface or in endosomes
genomic RNA is only PARTLY uncoated

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28
Q

RT, IN and some gag proteins remain associated with incoming ________

A

genomic RNA.

The proteins are needed to convert ssRNA→dsDNA via RT, nuclear import and integration

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29
Q

RT, IN and some gag proteins remain associated with incoming genomic RNA because:

A

reverse T and integrase are needed to convert ssRNA–>dsDNA as well as nuclear inport and integration

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30
Q

Do we start translation right after uncoating?

A

do NOT want to translate yet!!!! The protein particle prevents association of ribosomes… goal is to convert ssRNA→ dsDNA var RT

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31
Q

3rd step: Reverse Transcription: taking ssRNA→

A

dsDNA

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32
Q

During 3rd step: Integrated DNA (provirus) is longer then template RNA and has a U3 and U5 duplicated at the ends making the

A

Long Terminal Repeat or ‘LTR’

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33
Q

Reverse transcription accomplished in_______ via RT it brought along

A

cytoplasm

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34
Q

RT has 2 polymerase fnxs

A

a. RNA-dependent DNA polymerase (takes RNA→ DNA)

b. DNA-dependent DNA polymerase (copies 2nd strand of DNA from first strand)

35
Q

DNA-dependent DNA polymerase

part of RT

A

(copies 2nd strand of DNA from first strand)

36
Q

RNA-dependent DNA polymerase

part of RT

A

(takes RNA→ DNA)

37
Q

is an ‘error prone’ polymerase~ see 5 errors made per genome, allowing for rapid evolution and drug resistance

A

Reverse transcriptase

38
Q

What makes retrovises rapidly evolve and devo drug resistance

A

error prone polymerase (RT)

39
Q

_____ is KEY as TARGET for antiviral therapies, numerous inhibitors available for HIV (AZT therapy)

A

RT

40
Q

carried out bye integrase IN protein that enters cell w/ virus and stays associated w/ dsDNA

A

4th/5th step… Integration

41
Q

INtegration is carried out by IN in the protein that enters the cell w/ virus and:

A

stays associated with the dsDNA

42
Q

Integration requires dsDNA has access to ______;

A

host DNA

43
Q

many retroviruses can’t cross nuclear membrane and need cell division to integrate but HIV»»

A

HIV CAN cross nuclear env which is key for infecting nondividing cells and for gene therapies

44
Q

Integrase recognizes and is specific for sequences at the ends of dsDNA such as

A

U3 and U5

45
Q

Integration rxn is NOT specific for host sequences thus insertion is essentially______

A

random

but prefers to be near actively replicating genes

46
Q

_____alone performs insertion… makes it great therapeutic target

A

IN protein

47
Q

After integration….virus is ________resident of host cells DNA

A

PERMANENT

48
Q

6th step: Proviral Transcription: major role of LTR is to

A

direct synthesis of viral RNA

49
Q

what directs synthesis of viral RNA

A

LTR

50
Q

U3: has signal recognized by cell’s transcription machinery that directs transcription at beginning of ‘R’ region…but wait… they’re 2 U3 regions, how does it know????

A

a. while U3 is repeated at both ends, only 5’ LTR is transcriptionally active

51
Q

signal recognized by cell’s transcription machinery that directs transcription at beginning of ‘R’ region

A

U3

52
Q

.HIV LTR requires transcription factor of _____ that is only expressed in activated T cells…

A

NFkB

53
Q

reason why HIV RNA is not transcribed in infected memory T cells bc

A

memory cells do not express NFkB and HIV LRT requires it ot be activated

54
Q

7th step: RNA processing
as pol II transcripts, all viral RNAs are ______ and some must be sliced to generate
_______ while a large part aren’t because

A

polyadenylated,
env mRNA,
serve as a gag-pol mRNA and as genome for progeny virions

55
Q

Three fates of viral RNA
full length–>
full length–>
RNA splicing–>

A

Full length RNA → genomic RNA
Full length RNA → gag-pol mRNA
RNA splicing → all retroviruses make env mRNA (and others) by splicing: splicing is incomplete to preserve full-length RNA for genomic RNA and gag-pol mRNA

56
Q

gag-pol region is spliced our by

A

host splicesome

57
Q

Translation

1. Most abundant protein is _____and ____made as polyproteins form full length mRNA

A

gag and gag-pol,

58
Q

gag initiates____ start codon, ends at a stop codon,

A

AUG

59
Q

gag-pol made from same AUG start as gag, but ribosomes…..

A

‘ignore’ or circumvent the gag stop codon and continue to the end of pol.

60
Q

How often do ribosomes ignore gag stop codon

What does this result in

A

only happens about 5% of the time

RT and IN proteins are less abundant than gag

61
Q

Both gag and gag-pol proteins are eventually cleaved by________, releaseing ind proteins

A

protease PR domain

62
Q

Env protein made from spliced mRNA on ER-bound ribosomes, move through ER-golgi and

A

inserted into plasma membrane

63
Q

env gp160 precursor proteins is cleaved to

A

gp120 + gp41 by cellular protease

64
Q

Cleavage of gp160 MUST happen bc

A

gp 160 can’t support membrane fusion thus virus wouln’t be able o fuse with target cell`

65
Q

Virion assembly and budding involves what three steps

A

Packaging
Budding
Maturation

66
Q

Ky for Packaging;requires a signal, _____contained in unspliced but not spliced RNA

A

Psi

67
Q

What removes the psi signal

A

splicing

68
Q

Where is the psi signal contained

A

in the unspliced rna

69
Q

Budding—viral gag and gag-pol polyproteins recruit_____ and assemble______ cell surface

A

RNA

under

70
Q

During budding,

Gag proteins interact with env, and budding occurs as ______

A

particle forms

71
Q

Maturation:

causes protein rearrangements and the core to become _______

A

more dense

72
Q

proteolysis of gag and gag-pol by PR occurs

A

after budding

73
Q

During buddin: viral particles still form and bud if proteolysis is inhibited, but

A

viruses are not infectious

74
Q

Blocking thi step is the basis of HIV PR inhibitors

A

Maturation or budding

75
Q

Retroviruses discovered as agents isolated from naturally occuring tumors in animals– There wer inocculated to naïve animals→ see

A

they again cause tumors

76
Q

Non-transforming retroviruses: ‘non-acute’ or ‘slow’ tumor viruses
take _______ to appear

A

6 moths to a year

77
Q

Non-transforming retroviruses

A

do NOT transform cells in culture (low frequency and no ‘cancer’ phenotype’)
viruses do not contain oncogenes
tumors caused by activation or inactivation of host genes

78
Q

tumors caused by activation or inactivation of host genes (2 reasons)

A

a. promoter insertion: viral promoter used and see expression of unregulated protein or at wrong time
b. enhancer insertion: cell promoter inappropriately turned on→ correct protein made at wrong time

79
Q

Transforming retrovirus: or ‘acute’ virus

A
  1. infections case tumors w/in weeks

2. efficiently cause tissue culture cells to become ‘transformed’ or cancer-like

80
Q
  1. infections case tumors w/in weeks

2. efficiently cause tissue culture cells to become ‘transformed’ or cancer-like

A

transformning retrovirus or ‘acute’virus

81
Q

What did the transforming ‘acute’ retrovirus have to induce tumor onset

A

mutated copy of cellular gene involved in growth control, an ‘oncogene’
a. infection indroduce cancer causing gene, so see rapid tumor onset

82
Q

most oncogene containing viruses are defective bc

A

oncogene replaces one or more viral genomes

83
Q

Viruse have impact on cancer biology—d/t large number of oncogene identified
first oncogene idendified is____in the Rous sarcoma virus

A

(Src)

Immunology 3 (20 decks)

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