HIV Flashcards
HIV-1 genome is made up of structural and non structural genes. What do non structural genes control?
replication
where is the envelope around the virus derived from?
own cell membranes
large protein nuclear capsid structure inside the vireon is produced from what gene?
gag gene
what are the 2 main cellular targets for hiv?
cd4 lymphocytes and macrophages
where are cd4 lymphocytes localised ?
lymph nodes, GIT, other tissues
where are macrophages distributed?
all tissues and lymphatic system
what is the role of cd4 lymphocytes?
global immune helper cell
what is the role of macrophages?
phagocytosis and presenting foreign antigens within lymph nodes
What forms the trimer of receptors when viruses reach the surface of CD4 cells?
CCR5
CXCR4
CD4
some ppl have deletion in CCR5 so this means…
theyre naturally resistant to HIV
name 2 co receptors in close proximity to cd4 receptors that allow for hiv binding and virus entry?
CCR5 and CXCR4
as the gp41 and gp20 from the virus binds with cd4 receptors what happens, to allow for binding ?
conformational change to gp20 that allows interaction with CCR5, fusion takes place
post fusion, virus enters and nucelocapsid is within cell. Virus moves towards nuclus via microtubules in the cytoplasm. During this process, what enzyme starts to become active in the nucleo capsid?
reverse transcriptase
when the reverse transcriptase and RNAse H enzymes come into contact with the nucleus what process is commenced?
proviral dna synthesis and viral RNA digestion
..
so single RNA strand becomes RNA w a DNA template, RNA then degraded down -> another strand of DNA formed
when the nucelocapsid breaks down which dna is available at the nuclear pore?
proviral dsDNA
segments of proviral dsDNA is bounded to integrase enzyme. What is the role of this enzyme?
cuts proviral dsDNA, finds cellular dna and inserts proviral dna into our double stranded dna
post integration proviral dna is inserted into our dna. proviral dna may remain dormant and later be reactivated via cellular transcription pathways.
If reactivated, what is generated from cellular dna?
viral mRNA
true or false: viral rna is looped and spliced to different lengths?
true
what is the role of the cell protein TAT?
directs viral mrna to leave nucleus via nuclear pores
what different things can happen to viral mrna when it leaves the nucleus?
some goes to ribosomes and used as templates for hiv protein synthesis like gag and some form stable dimer of 2 copies as new viral genome
what causes infected cell surfaces to start to bulge?
new viral proteins and gag pack together with viral genome
once the surface of an infected cell membrane starts to bulge, proteins are recruited and pull together the virion and protease enzymes. What process do these catalyze?
viral protein cleavage into functional units
what is closure facilitated by to allow the virus to bud off from the cd4 cell?
specific contractile proteins that draw the neck together
p655 summary of hiv1 life cycle
what are NRTIS?
nucleoside reverse transcriptase inhibitors
How do nucleoside reverse transcriptase inhibitors work?
Prevents viral replication.
NRTIS are incorporated into dna chains and act as X to prevent replication?
chain terminators
How do non-nucleoside reverse transcriptase inhibitors work? NNRTIs
bind to and block HIV reverse transcriptase
How do integrase inhibitors work?
Prevents viral DNA being integrated with the host cellular DNA
fast reductions in HIV viral load
How do protease inhibitors work?
Prevents processing and packaging of viruses before release from the lymphocyte.
what does success of HIV relate to?
enormous viral replicative capacity (new gen per 1-4 hrs)
each gen archived in memory cells
Why do viruses not produce identical replicas?
Reverse transcriptase is very error prone and lacks a proof-reading function.
slight mutations causes new viral cells.
what allows real-time evolution of viral cells to changing environmental pressures in the host?
mutated viral replicas are archived in memory cells.
what are the 3 types of mutations?
neutral
deleterious
advantageous
whats a codon?
3 bases = 1 aa
the evoluation of an advantageous virus is a process of selection under what pressure?
environmental
eg BP
we take plasma virions to test for hiv, what is the half life?
6hrs
true or false primary infection (PHI) involves 1 or 2 genetic types?
true
majority of virions are produced via which pool?
productively infected
activated CD4 lymphocytes
t1/2 2.2 days
follicular DC t1/2?
14 days (longer)
virus gets incorporated into cells DNA but dont become activated + can become dormant and cause extremely long lived popns with extrememly long…
t1/2
what is meant by viral quasispecies?
multiple rounds of replication, viral genetic errors, (due to absence of proof reading)
VQ = daughter viruses genetically distinct, archived in memory cells, portfolio of thousands of genetically related viruses
in acute infection is the viral population homogenous or heterogenous?
homogeneous
in established infection is the viral population homogenous or heterogenous?
heterogeneous
every single mutation that can cause drug resistance alr pre-exists in a chronically infected px
T/F?
True
we give drugs not fully suppressive to select out those mutations alr present
over time as genetic diversity increases, how does VL viral load change?
decreases
high diversity, low VL
What are the 3 main pathways to persistent viral replication then -> drug failure in HIV?
drug resistance
sub-inhibitory drug levels
host immune failure
On what two bases can drug resistance occur in patients?
pre-exists
selected by drug
give 2 ways that drug resistant varients can pre exist in patients?
transmitted or drug independent evolution
how does persistant viral replication lead to drug failure?
evolution of drug resistance
name 2 factors that lead to sub inhibitory drug levels?
pharmacological issues
or poor adherence
2 types of selected drug resistance, regarding virus
selected or transmitted drug resistance
what is meant by wt virus?
no drug resistant mutations
outline how selected drug resistance works and can be lead to an emergence of wt virus after discontinuing therapy?
initial wt virus -> resistant variants selected during therapy -> rapid reemergence of wt virus upon discontinuing therapy
in selected drug resistance - with continued presence of drugs, the resistant variant (WT) become what?
dominant quasispecies
->reemergence of WT virus