Key Players
What is the viral polyprotein that coordinates HIV-1 assembly to suppress inappropriate protease (PR) activity?
Gag
What is the pro-inflammatory cytokine whose secretion is a measurable result of CARD8 inflammasome activation
IL-1B
What is the Gag domain whose disruption, ΔMA6-125, led to a significant increase in IL-1B secretion compared to wild-type virus?
Matrix (MA)
What happens in terms of IL-1B secretion when when Gag/Gag-pol cannot localize to the plasma membrane?
Pro-IL-1B is not cleaved and IL-1B is not secreted
What is the HIV-1 enzyme whose untimely activation is sensed by CARD8, leading to inflammasome formation?
HIV-Protease (PR)
What is the type of programmed inflammatory cell death that is initiated by the formation of the CARD8 inflammasome?
Pyroptosis
What was the effect on IL-1B secretion of the myristoylation-deficient MA mutant, G2A, which attenuates membrane association of Gag?
Abrogated IL-1B secretion
What is the sensor activated during MA-deficient virus assembly in HEK293T cells and PMA/THP macrophages?
CARD8
What is the Gag domain where host-adaptive mutations, such as M30K, are associated with greater fitness and evasion of pyroptotic cell death?
Matrix (MA)
While activation of the CARD8 inflammasome may be beneficial as it leads to pyroptosis of infected cells, what is a consequence that is detrimental to the human host?
Pyroptosis leads to the mass death of CD4+ T cells
What is the name of the HIV-1 protease inhibitor that completely restored survival of GFP+ cells that were infected with MA6-125
SQV
PR was able to leak out of the budding virion, leading to greater CARD8 activation
What Gag domain is responsible for ESCRT recruitment and timely virus particle budding?
p6
The release of this molecule indicates that pyroptosis has occurred and cytoplasmic contents have leaked from the cell.
LDH
What editing technique was used to disrupt the open reading frame of CARD8 in the experiment investigating the sensor responsible for inflammasome activation?
CRISPR
Why was there a near-universal adaptation in MA during zoonotic transformation of SIVcpz to HIV-1
New encounter of CARD8 immune pressure in human cells