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Biomed 2 - Season finale > III - HIV > Flashcards

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
Q

what happens after gp120 binds to a chemokine receptor

A

gp41 released from high energy state
fusion peptide springs out towards host cell membrane
bridging gap between virion/host cell membrane

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26
Q

what does expression of the mutated CCR5 allele cause

A

non-functional form of CCR-5 protein
delays progression to AIDS

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27
Q

if someone is infected with HIV but their CXCR-4 is normal, what does this suggest

A

infection via M-tropic variants using CCR-5 receptors

28
Q

what does emergence of T-tropic variants indicate

A

sign of rapid progression into AIDS

29
Q

what does the fusion between the virus and the host cell mediated by gp41 allow

A

viral nucleocapsids to enter the cell

30
Q

what happens once the nucleocapsid enters the cell

A

nucleocapsid is removed
reverse transcriptase copies RNA to dsDNA

31
Q

what is a feature of viral reverse transcriptase in the host

A

poor fidelity
no proof reading
10 mistakes per replication round
many mutations arise

32
Q

what is a prerequisite for a provirus

A

viral DNA integrates into the host cell DNA

33
Q

following HIV infection, what does histological examination of the lymph nodes show

A

disruption of lymph node architecture
influx of CD8-T cells
eventual loss of germinal centres

34
Q

how does HIV get to the lymph nodes

A

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
Q

how do dendritic cells recognise HIV for uptake

A

sialylactose head on GM3 ganglioside exposed on HIV membrane
recognised by dendritic cell for uptake

36
Q

how does HIV infection effect CD4 cell function

A

induces loss of function in CD4 T cells

37
Q

what do HIV infected individuals show increased levels

A

serum Ig
autoantibodies for RBC, sperm, myelin

38
Q

what is the antibody immune response to HIV infection

A

strong antibody response to
gp120 and p24

39
Q

what is the T cells immune response to HIV infection

A

CD8 cytotoxic cells against
gp120, p24 and some reverse transcriptase machinery

40
Q

why is it inaccurate to state that the virus is only in a provirus and inactive state during the latent phase

A

there is a persistent level of active viral replication found even in latent phases

41
Q

what is the difference in the levels of infection of CD4 cells in the blood than the lymph nodes

A

10-100x times more productively infected in the lymph nodes than the blood

42
Q

what are the reasons why the immune system cannot remove HIV

A

very high replication rate
can hide as a provirus where it will not be detected
very high mutation rate - antigens keep changing

43
Q

what viral antigens may infected CD4 cells present

A

viral peptides presented by MHC class 1
soluble gp120 bound to CD4

44
Q

what does soluble gp120 bind to

A

CD4 T cells

45
Q

outline the antibody-complement CD4 killing mechanism

A

anti-gpl20 binds to gp120 bound to CD4
causes complement fixation and activation
results in cell lysis

46
Q

outline the antibody dependent cell mediated cytotoxicity CD4 killing mechanism

A

macrophages and NK cells possess Fc receptors
able to bind to Fc portion of anti-gpl20 antibody bound to CD4
kills the cell

47
Q

what happens when HIV infects permissive CD4 cells in the spleen

A

apoptosis via caspase-3

48
Q

what happens when HIV abortively infects non-permissive CD4 cells

A

death by pyroptosis
via capsase-1 activation

49
Q

what does inefficient reverse transcriptase in these cells lead to

A

leads to cytoplasmic accumulation of viral DNA
detected by DNA sensors - IFI16
results in inflammasome assembly
caspase-1 activity
pyroptosis

50
Q

what makes blood derived CD4 T cells more resistant to pyroptosis

A

deeper resting state
fewer HIV-1 reverse transcriptase
lower IFI16 expression

51
Q

what happens when blood derived CD4 becomes co-cultured with lymphoid-derived cells and why

A

CD4 cells become sensitised to pyroptosis
higher levels of NF-kB, IFI16 and reverse transcriptase

52
Q

what was the first anti-HIV drug

A

zidovudine
a reverse transcriptase inhibitor

53
Q

what are the categories of HIV inhibitors

A

nucleoside analogue reverse transcriptase inhibitors
non-nucleoside analogue reverse transcriptase inhibitors
HIV protease inhibitors

54
Q

how does nucleotide analogue block viral DNA synthesis and what is this called

A

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
Q

how does non-nucleoside analogue reverse transcriptase inhibit viral DNA synthesis and what is it called

A

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
Q

function of protease inhibitors as HIV medication and how

A

inhibit active site of HIV aspartic protease
peptide linkage is replaced by uncleavable hydroxyethylene group

57
Q

function of HIV aspartic protease

A

cleaves a number of viral polyproteins to produce a number of HIV proteins and enzymes

58
Q

what does combination chemotherapy consist of

A

2 reverse transcriptase inhibitors
1 protease inhibitor

59
Q

what does HIV Vif degrade

A

interferon-α JAK/STAT1 and 3 pathway

60
Q

what is the difference between a prophylactic/therapeutic vaccines

A

prophylactic - used to prevent AIDS
therapeutic - used to treat aids via boosting patient immune system

61
Q

difference between an obligate and facultative parasite

A

obligate - requires host to complete life cycle
facultative - doesn’t require host to complete life cycle

62
Q

definition of an endoparasite

A

all those that live inside the host - parasitic worms

63
Q

what 3rd organism do endoparasites usually require

A

a vector

64
Q

where do tapeworms (cestodes) reside

A

brain
eye
muscles
skin

65
Q

where do flukes (trematodes) reside

A

blood vessels

66
Q

where do roundworms (nematodes) reside

A

pulmonary artery

Biomed 2 - Season finale (24 decks)

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