HIV (Dr. Cochrane) Flashcards
(56 cards)
Origin of HIV?
from SIVcpz of chimpanzees
What happens when old world monkeys have HIV-1?
High level of viremia
BUT not immune deficiency
Differences between SIV infection in human in natural host
I) Level of peripheral CD4+ T cells:
Healthy in host, low in humans
II) immune dysfunction: only found in human
III) chronic immune activation: only in human
Factors affecting transmission efficiency
I) inflammation due to other infections increase number of target cells in mucus, mucosal envrionment
II) viral load in inoculum
Types of HIV-1
R5, X4
Which form can transmit acroos mucosal membrane?
R5
Site of SIV-1 replication?
Gastrointestinal tract
Nasal cavity
Male genital tract
Lymph nodes
Lungs
Cells infected by HIV-1
I) CD4+ T cells
II) Monocytes/macrophages
What happens after CD4+ T cell infected by HIV-1?
Infected cells can induce death of neigbouring T cells by pyroptosis due to abortve infection
What happens after macrophages are infected by HIV-1?
Can enhance HIV-1 infection of surrounding cells
what decides the progression of HIV infection/
Viral load setpoint
—> the higher, the quicker it reaches end pt
Why current treatments unable to cure HIV-1
I) residual levels of viral replication (not fully suppressed)
II) small pool of cells with silent integrated genomes persist
III) persistent immune dysfunctions
What co-receptor do X4 bind for entry?
CXCR4
What co-receptor does R5 bind to?
CCR5
How does HIV-1 enter our cells?
I) bind to CD4 —> change in gp120 on virus
II) change in gp120 allow binding to secondary receptor (CXCR4/CCR5)
A genetic mutation that led to HIV-1 resistance
Lacking CCR5
What happens during clinical latency that complicates cure?
Lots of new virions formed per day (2 billion)—> kill equal number of T cells
—> lots of new mutation arise, huge variety in HIV-1
What is HIV-1/2 transcription dependent on?
Activation state of cell (must be activated)
Why is HIV-1 most active in T cells?
Active NFAT, NFkappaB, AP2 present only in activated T cells
How does HIV-1 exploit adaptive immune system?
Once T cells activated, HIV-1 can infect it
—> can integrate into memory T cells
—> oncre reactivated —> able to expand and replicate new virions
How does viral insertion into cell DNA + long living infected cells affect treatment?
I) no idea where the reservoir is + reservoir established 3 days after exposure
II) take long time for treatment as those with silent virus are not killed thru drugs (take 60 years)
III) withdrawal of drugs —> infection reappear rlly quick
Approaches suggested to kill HIV
I) Shock and kill
II) enhance function of immune system
III) Scorched earth
IV) Block and lockH
How does shock and kill work?
Use agents to force cells to express latent virus —> immune system can detect and kill
How does scorched earth work?
Wipe out all immune cells and replace with new ones resistant to virus