III - HIV Flashcards

1
Q

what is the structure of the HIV genome

A

contains 2 molecules of ssRNA
bound by reverse transcriptase

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2
Q

what p enzymes does the HIV genome contain

A

p35 integrase
p10 protease

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3
Q

what is the genome surrounded by

A

nucleocapsid:
inner layer - protein p24
outer layer - protein p17

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4
Q

what does the outer portion of the HIV virus consist of

A

a lipid envelope derived from the host cell membrane

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5
Q

what are the viral envelope proteins

A

gp120
gp41

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6
Q

what does HIV GAG encode, what does it produce and processes it

A

encodes structural capsid proteins
produces GAG precursor polyprotein
is processed by viral protease

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7
Q

life cycle of HIV step 1

A

virus binds to CD4 via gp120-CD4 interaction

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8
Q

life cycle of HIV step 2

A

nucleocapsid enters the cell
releases viral RNA
viral RNA is reverse transcribed into dsDNA

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9
Q

life cycle of HIV step 3

A

viral DNA integrated with the host genome and lays dormant as a provirus

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10
Q

life cycle of HIV step 4

A

after cell activation
viral DNA directs the transcription of viral RNA

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11
Q

life cycle of HIV step 5

A

viral protein are translated from the viral RNA

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12
Q

life cycle of HIV step 6

A

viral proteins and viral ssRNA assemble to form new viral particles

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13
Q

life cycle of HIV step 7

A

virus buds off of host cell, taking some membrane with it
complete viral particle can now infect other cells

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14
Q

binding of g120 to CD4 is not enough for HIV to infect cells, what else is required for them to invade

A

gp41 binds to second protein on cell surface
second protein differs depending on HIV variant

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15
Q

what does the gp41 of M-tropic HIV variants bind to

A

β-chemokine receptor CCR-5
located on the cell surface off monocytes and dendritic cells

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16
Q

what does M-tropic HIV variants infect

A

monocytes and dendritic cells

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17
Q

what do T-tropic HIV variants bind to

A

α-chemokine receptor - CXCR-4
present of CD4 T cells

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18
Q

what do T-tropic HIV variants only infect

A

T cells

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19
Q

what is gp160

A

its a fusion glycoprotein to overcome the energy barrier associated with the fusion of 2 membranes

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20
Q

structure of gp160

A

trimer formation - 3 molecules of gp160 are arranged together
aka - spikes

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21
Q

what does gp160 cleave into

A

gp41
gp120

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22
Q

what are gp41 and gp120

A

gp41 - transmembrane glycoprotein
pg120 - surface glycoprotein

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23
Q

what state does gp41/120 remain in and what implications does this have

A

they remain in a trimeric state
non-covalently bound to each other
gp41 is in high energy state and
fusion peptide buried inwards

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24
Q

what does gp120 bind to and what does it cause

A

binds to host cell surface CD4 receptor
gp120 conformational change
gp120 able to bind to chemokine receptors
usually - CXCR4/CCR5

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25
what happens after gp120 binds to a chemokine receptor
gp41 released from high energy state fusion peptide springs out towards host cell membrane bridging gap between virion/host cell membrane
26
what does expression of the mutated CCR5 allele cause
non-functional form of CCR-5 protein delays progression to AIDS
27
if someone is infected with HIV but their CXCR-4 is normal, what does this suggest
infection via M-tropic variants using CCR-5 receptors
28
what does emergence of T-tropic variants indicate
sign of rapid progression into AIDS
29
what does the fusion between the virus and the host cell mediated by gp41 allow
viral nucleocapsids to enter the cell
30
what happens once the nucleocapsid enters the cell
nucleocapsid is removed reverse transcriptase copies RNA to dsDNA
31
what is a feature of viral reverse transcriptase in the host
poor fidelity no proof reading 10 mistakes per replication round many mutations arise
32
what is a prerequisite for a provirus
viral DNA integrates into the host cell DNA
33
following HIV infection, what does histological examination of the lymph nodes show
disruption of lymph node architecture influx of CD8-T cells eventual loss of germinal centres
34
how does HIV get to the lymph nodes
it hitches a ride on dendritic cells that surveillance the area but does not get killed and hitches a ride to the lymph nodes before transfer to the CD4 cells
35
how do dendritic cells recognise HIV for uptake
sialylactose head on GM3 ganglioside exposed on HIV membrane recognised by dendritic cell for uptake
36
how does HIV infection effect CD4 cell function
induces loss of function in CD4 T cells
37
what do HIV infected individuals show increased levels
serum Ig autoantibodies for RBC, sperm, myelin
38
what is the antibody immune response to HIV infection
strong antibody response to gp120 and p24
39
what is the T cells immune response to HIV infection
CD8 cytotoxic cells against gp120, p24 and some reverse transcriptase machinery
40
why is it inaccurate to state that the virus is only in a provirus and inactive state during the latent phase
there is a persistent level of active viral replication found even in latent phases
41
what is the difference in the levels of infection of CD4 cells in the blood than the lymph nodes
10-100x times more productively infected in the lymph nodes than the blood
42
what are the reasons why the immune system cannot remove HIV
very high replication rate can hide as a provirus where it will not be detected very high mutation rate - antigens keep changing
43
what viral antigens may infected CD4 cells present
viral peptides presented by MHC class 1 soluble gp120 bound to CD4
44
what does soluble gp120 bind to
CD4 T cells
45
outline the antibody-complement CD4 killing mechanism
anti-gpl20 binds to gp120 bound to CD4 causes complement fixation and activation results in cell lysis
46
outline the antibody dependent cell mediated cytotoxicity CD4 killing mechanism
macrophages and NK cells possess Fc receptors able to bind to Fc portion of anti-gpl20 antibody bound to CD4 kills the cell
47
what happens when HIV infects permissive CD4 cells in the spleen
apoptosis via caspase-3
48
what happens when HIV abortively infects non-permissive CD4 cells
death by pyroptosis via capsase-1 activation
49
what does inefficient reverse transcriptase in these cells lead to
leads to cytoplasmic accumulation of viral DNA detected by DNA sensors - IFI16 results in inflammasome assembly caspase-1 activity pyroptosis
50
what makes blood derived CD4 T cells more resistant to pyroptosis
deeper resting state fewer HIV-1 reverse transcriptase lower IFI16 expression
51
what happens when blood derived CD4 becomes co-cultured with lymphoid-derived cells and why
CD4 cells become sensitised to pyroptosis higher levels of NF-kB, IFI16 and reverse transcriptase
52
what was the first anti-HIV drug
zidovudine a reverse transcriptase inhibitor
53
what are the categories of HIV inhibitors
nucleoside analogue reverse transcriptase inhibitors non-nucleoside analogue reverse transcriptase inhibitors HIV protease inhibitors
54
how does nucleotide analogue block viral DNA synthesis and what is this called
analogue lacks 3'hydroxyl group on deoxyribose prevents incoming nucleotide from forming a 5'-3' phosphodiester bond viral DNA synthesis is halted competitive substrate inhibition
55
how does non-nucleoside analogue reverse transcriptase inhibit viral DNA synthesis and what is it called
non-nucleoside analogue binds to enzyme not incorporated into the DNA tampers with reverse transcriptase machinery required for its function prevents viral DNA synthesis non-competitive substrate inhibition
56
function of protease inhibitors as HIV medication and how
inhibit active site of HIV aspartic protease peptide linkage is replaced by uncleavable hydroxyethylene group
57
function of HIV aspartic protease
cleaves a number of viral polyproteins to produce a number of HIV proteins and enzymes
58
what does combination chemotherapy consist of
2 reverse transcriptase inhibitors 1 protease inhibitor
59
what does HIV Vif degrade
interferon-α JAK/STAT1 and 3 pathway
60
what is the difference between a prophylactic/therapeutic vaccines
prophylactic - used to prevent AIDS therapeutic - used to treat aids via boosting patient immune system
61
difference between an obligate and facultative parasite
obligate - requires host to complete life cycle facultative - doesn't require host to complete life cycle
62
definition of an endoparasite
all those that live inside the host - parasitic worms
63
what 3rd organism do endoparasites usually require
a vector
64
where do tapeworms (cestodes) reside
brain eye muscles skin
65
where do flukes (trematodes) reside
blood vessels
66
where do roundworms (nematodes) reside
pulmonary artery