III - HIV Flashcards
what is the structure of the HIV genome
contains 2 molecules of ssRNA
bound by reverse transcriptase
what p enzymes does the HIV genome contain
p35 integrase
p10 protease
what is the genome surrounded by
nucleocapsid:
inner layer - protein p24
outer layer - protein p17
what does the outer portion of the HIV virus consist of
a lipid envelope derived from the host cell membrane
what are the viral envelope proteins
gp120
gp41
what does HIV GAG encode, what does it produce and processes it
encodes structural capsid proteins
produces GAG precursor polyprotein
is processed by viral protease
life cycle of HIV step 1
virus binds to CD4 via gp120-CD4 interaction
life cycle of HIV step 2
nucleocapsid enters the cell
releases viral RNA
viral RNA is reverse transcribed into dsDNA
life cycle of HIV step 3
viral DNA integrated with the host genome and lays dormant as a provirus
life cycle of HIV step 4
after cell activation
viral DNA directs the transcription of viral RNA
life cycle of HIV step 5
viral protein are translated from the viral RNA
life cycle of HIV step 6
viral proteins and viral ssRNA assemble to form new viral particles
life cycle of HIV step 7
virus buds off of host cell, taking some membrane with it
complete viral particle can now infect other cells
binding of g120 to CD4 is not enough for HIV to infect cells, what else is required for them to invade
gp41 binds to second protein on cell surface
second protein differs depending on HIV variant
what does the gp41 of M-tropic HIV variants bind to
β-chemokine receptor CCR-5
located on the cell surface off monocytes and dendritic cells
what does M-tropic HIV variants infect
monocytes and dendritic cells
what do T-tropic HIV variants bind to
α-chemokine receptor - CXCR-4
present of CD4 T cells
what do T-tropic HIV variants only infect
T cells
what is gp160
its a fusion glycoprotein to overcome the energy barrier associated with the fusion of 2 membranes
structure of gp160
trimer formation - 3 molecules of gp160 are arranged together
aka - spikes
what does gp160 cleave into
gp41
gp120
what are gp41 and gp120
gp41 - transmembrane glycoprotein
pg120 - surface glycoprotein
what state does gp41/120 remain in and what implications does this have
they remain in a trimeric state
non-covalently bound to each other
gp41 is in high energy state and
fusion peptide buried inwards
what does gp120 bind to and what does it cause
binds to host cell surface CD4 receptor
gp120 conformational change
gp120 able to bind to chemokine receptors
usually - CXCR4/CCR5
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
what does expression of the mutated CCR5 allele cause
non-functional form of CCR-5 protein
delays progression to AIDS
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
what does emergence of T-tropic variants indicate
sign of rapid progression into AIDS
what does the fusion between the virus and the host cell mediated by gp41 allow
viral nucleocapsids to enter the cell
what happens once the nucleocapsid enters the cell
nucleocapsid is removed
reverse transcriptase copies RNA to dsDNA
what is a feature of viral reverse transcriptase in the host
poor fidelity
no proof reading
10 mistakes per replication round
many mutations arise
what is a prerequisite for a provirus
viral DNA integrates into the host cell DNA
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
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
how do dendritic cells recognise HIV for uptake
sialylactose head on GM3 ganglioside exposed on HIV membrane
recognised by dendritic cell for uptake
how does HIV infection effect CD4 cell function
induces loss of function in CD4 T cells
what do HIV infected individuals show increased levels
serum Ig
autoantibodies for RBC, sperm, myelin
what is the antibody immune response to HIV infection
strong antibody response to
gp120 and p24
what is the T cells immune response to HIV infection
CD8 cytotoxic cells against
gp120, p24 and some reverse transcriptase machinery
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
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
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
what viral antigens may infected CD4 cells present
viral peptides presented by MHC class 1
soluble gp120 bound to CD4
what does soluble gp120 bind to
CD4 T cells
outline the antibody-complement CD4 killing mechanism
anti-gpl20 binds to gp120 bound to CD4
causes complement fixation and activation
results in cell lysis
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
what happens when HIV infects permissive CD4 cells in the spleen
apoptosis via caspase-3
what happens when HIV abortively infects non-permissive CD4 cells
death by pyroptosis
via capsase-1 activation
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
what makes blood derived CD4 T cells more resistant to pyroptosis
deeper resting state
fewer HIV-1 reverse transcriptase
lower IFI16 expression
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
what was the first anti-HIV drug
zidovudine
a reverse transcriptase inhibitor
what are the categories of HIV inhibitors
nucleoside analogue reverse transcriptase inhibitors
non-nucleoside analogue reverse transcriptase inhibitors
HIV protease inhibitors
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
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
function of protease inhibitors as HIV medication and how
inhibit active site of HIV aspartic protease
peptide linkage is replaced by uncleavable hydroxyethylene group
function of HIV aspartic protease
cleaves a number of viral polyproteins to produce a number of HIV proteins and enzymes
what does combination chemotherapy consist of
2 reverse transcriptase inhibitors
1 protease inhibitor
what does HIV Vif degrade
interferon-α JAK/STAT1 and 3 pathway
what is the difference between a prophylactic/therapeutic vaccines
prophylactic - used to prevent AIDS
therapeutic - used to treat aids via boosting patient immune system
difference between an obligate and facultative parasite
obligate - requires host to complete life cycle
facultative - doesn’t require host to complete life cycle
definition of an endoparasite
all those that live inside the host - parasitic worms
what 3rd organism do endoparasites usually require
a vector
where do tapeworms (cestodes) reside
brain
eye
muscles
skin
where do flukes (trematodes) reside
blood vessels
where do roundworms (nematodes) reside
pulmonary artery
