L6 - HIV (2) Flashcards
What are the 3 ORFs of HIV?
Gag
Pol
Env
How are HIV-1 and HIV-2 different?
vpx instead of vpu
Why is HIV so complex?
Enable replication and persistence in adult host
enabled cross-species transmission
What happens to CD4 cells when AIDS develops?
CD4 and CTL count drops
What is the half life of cells infected with HIV?
<2 days
10^10 virions produced per day
What kind of latency does HIV have?
CLINICAL!
NOT cellular
What is the balance shift of clinical latency?
more CD4 cells killed than produced
destroy lymph node
immune system weakened and overwhelmed
What are symptoms of HIV primary infection?
mononucelosis-like syndrome
fever, malaise, rash, diarrhoea
What are symptoms of clinical latency?
often NO symptoms
sometimes fatigue, weight loss, thrush, shingles
What happens when CD4 cell number per ul are 200-500?
shingles oral lesions tb M. contagiosum C. acuminata
What happens when CD4 cell number per ul are LESS THAN 200?
protozoal - pneumocytis carinii
Bacterial - T. pallidum
Fungal - C. albicans, C neoformans
Viral - CMV, HSV EBV, KSHV
What is ADC?
AIDS dementia complex
infection of brain macrophages and glial cells
What do Th1 cells produce and what do the chemokines activate?
produce IL-2, IL-12, IFN-y
activate CD8+ CTLs
What do Th2 cells produce and what do the chemokines activate?
IL-4, IL-10
B-lymphocytes - humoral immune system
What cell produces Th1 and Th2 cells?
CD4+ T-helper cells
What cells are atrgetted by HIV?
Monocytes
precursors to APCs
Macrophages
Dendritic cells
How does HIV get into cells?
gp120 structure changes to bind to co-receptor chemokine
induces change in gp41
expose fusion domain
membranes fuse
What are the 2 HIV receptors
CD4 - PRIMARY
Chemokine - alpha (CxC) or beta (CC)
What part of HIV interacts with Chemokine receptor?
V3 loop
binds to heparan sulphate prior to binding
What chemokine receptor is used in early HIV infection?
B-chemokine - CCR5
R5 viruses
NON-SYNCYTIUM INDUCING - DO NOT FUSE CELLS
What chemokine receptor is used in later infection (AIDS)?
a-chemokine - CXCR4
X4 viruses
SYNCYTIUM INDUCING
How does the receptor for HIV change?
mutation of V3 loop of gp120 - amino acid change allows different binding
What cells do R5 viruses infect (HIV)?
Macrophage
T cells
What cells to X4 viruses infect
(MEMORY) T-cells
what is the deletion that allows HIV resistance?
32bp deletion in CCR5 gene
STILL hav CxCR4 genes though
What is the role of dendritic cells in HIV infection?
picked up by dendritic cells
migrates to lymph node
How can HIV associate with dendritic cells?
DC-SIGN
usually binds ICAM-3 on surface of T-cells
lectin domain binds to the carbohydrate on the HIV glycoprotein
Can HIV infect dendritic cells?
Yes are they have CCR5 receptor in membrane
How does HIV get from Dendritic cells to T cells?
virological synapse with adhesive junction
How does a virological synapse form between T-cells?
requires gp:120:CD4/CCR5 interactions
clusters of receptors
avoids the immune response and damage to virus particles
