L68 Flashcards
What is the family & genus of HIV?
Family = retrovirus (RNA –> DNA)
Genus - lentivirus (long incubation time)
What does a high error rate of reverse transcriptase yield?
HIV evolution –> drug resistance
What are the 2 important proteins of the HIV envelope?
Gp120 + gp41 = spike
Coded from env
What is gag p17?
Matrix
Lines inner leaflet of envelope
What is gag p24?
The capsid that encloses HIV RNA + enzymes + proteins
Which enzymes are carried with HIV in active form?
= regulatory proteins
- Reverse transcriptase - to code DNA once inside host cell
- Integrase - follows RT
- Protease - was used to mature the virion after budding
What is the diagnostic marker used to measure the effectiveness of anti-retroviral therapies?
HIV RNA gag p24 (capsid)
What part of HIV is the therapeutic target?
The enzymes!
Kill these - make the virus ineffective
What are modes of HIV transmission?
Sex
During birth
Needles! IVDUs
How does HIV get into tissues?
- Break mucosal epi barrier
- Transcytosis
Either way = bad b/c 1st responder likely to be CD4 = infection target
How does HIV attach to host cells?
Gp41/120 spike + CD4
Conformational change –> membranes together
What is required for HIV-host membrane fusion?
Co-receptor binding (by different part of gp120)
CCR5 and/or CXCR4
- Found on macrophages & T cells (cell trophism)
MEANS that entry requires TRIMER formation: gp41/120 + CD4 + co-receptor
What is the pre-integration complex vs provirus?
Pre-integration complex = how enters nucleus w/ integrase
Provirus = after in host DNA
How can genetics or drugs affect HIV by working at CCR5?
Genetics:
- Mutated –> no CCR5 fxn but also no HIV co-receptor needed for binding
Drug target - Maraviroc
What are the 3 types of RT inhibitors?
Nucleoside analogs
NucleoTIDE analogs
Non-nucleoside analogs
All 3 change RT’s fxn = X RNA –> DNA
What are HIV long terminal repeats (LTRs)?
Identical RNA on both ends (5 & 3’) of the genome
Used for integration
Where do transcription factors that regulate expression of viral genes bind?
@ 5’ LTR
What are the 3 classes of RNA molecules produced during viral replication? Which are packaged into the virus?
2kb, 4kb - 9kb into new virus
Which RNA protein is used to make the initial HIV diagnosis?
gag p24
What are the 3 structural genes on the RNA genome?
Gag (non-envelope membranes)
Pol (polymerases)
Env (envelope)
What 2 proteins are coded for by the gag gene?
gag p24 = capsid
gag p17 = matrix, lines inner leaflet of viral envelope
What 3 proteins are coded for by the pol gene?
RT
Integrase
Protease
What 3 proteins are coded for by the env gene?
gp 120 & 41
What are the 2 regulatory genes of the HIV genome?
Tat - needed for initiation & elongation starting at 5’ LTR
Rev - transports new virion RNA into the cytoplasm
What are the 4 accessory proteins/genes on the HIV genome?
nef vpr vpu vif As a group, remove restriction factors that host cell uses to stop DNA replication when senses infection
Which cells can HIV target to change function and create immune deficiency?
CD 4 & CD8 T cells B cells Myeloid DCs Plasmacytoid DCs Uninfected bystander cells
What is pyroptosis?
HIV induced cell death that is VERY inflammatory
Recruits other immune cells –> prime for infection
What is the viral load?
In acute infection, when virus in plasma peaks
What is the viral set point?
When CD8 response rises to control viral replication
- Allows recruitment of Ab response
How can HIV infected cells kill uninfected bystanders?
Infected - normal
CD95L - CD95
gp41/120 - CD4/CXCR4 death signals
Which 2 cytokines have anti-HIV properties?
IL10
IFNg
Which HLA subtypes have natural protection against HIV?
B 27 & 57
Describe the T cell HIV vaccine.
Infect APCs to present HIV to T cells –> create stronger immune response if the virus actually presents
Problem = Too late, could have already est infection in APCs
More therapeutic
Describe the B cell HIV vaccine?
Abs vs gp 41/120 - no initial binding & prevent 1ary infection
Problem: HIV variation & getting Abs that are long lasting in high [ ]s
What are the 2 major HIV vaccine trials?
STEP = T cell vaccine, failure, increased infection
RV144 Thai = B cell vaccine, saw 31% less infection
