Fig. 3.

Pyroptosis signalling in virus infection.

NLRP3 can be activated by various insults, including potassium efflux, extracellular ATP, and binding of virus associated patterns to host proteins (P2X4, CLEC5A, galectins). Activation of NLRP3 leads to the assembly of ASC specks, resulting in caspase-1 activation. vDNA is engaged by AIM2 resulting in ASC speck formation. Aberrant DNA fragments produced by HIV is recognized by IFI-16, which initiates caspase-1 activation. Active caspase-1 accomplishes the processing of GSDMD and pro-IL1β/ pro-IL18. Cleaved GSDMD oligomers form pores in the cytoplasm membrane. The mature ILs are released to the extracellular space throughout the GSDMD pores and the pore formation culminates in membrane ruptures and osmotic imbalances, ultimately leading to a lytic cell death, called pyroptosis.