Regulation of innate immune responses by cell death‐associated caspases during virus infection

Abstract

Viruses are obligate intracellular pathogens that rely on cellular machinery for successful replication and dissemination. The host cells encode a number of different strategies to sense and restrict the invading viral pathogens. Caspase‐mediated programmed cell death pathways that are triggered by virus infection, such as apoptosis and pyroptosis, provide a means for the infected cells to limit viral proliferation, leading to suicidal cell death (apoptosis) or lytic cell death and alerting uninfected cells to mount anti‐viral responses (pyroptosis). However, some viruses can employ activated caspases to dampen the anti‐viral responses and facilitate viral replication through cleavage of critical molecules of the innate immune pathways. The regulation of innate immune responses by caspase activation during virus infection has recently become an important topic. In this review, we briefly introduce the characteristics of different classes of caspases and the cell death pathways regulated by these caspases. We then describe how viruses trigger or dampen caspase activation during infection and how these activated caspases regulate three major innate immune response pathways of viral infections: the retinoic acid‐inducible gene I‐like receptor, toll‐like receptor and cyclic GMP‐AMP synthase‐stimulator of interferon genes pathways.

Caspase activation counteracts interferon signaling after G2 checkpoint abrogation by ATR inhibition in irradiated human cancer cells

“…Our finding, that caspase inhibition increases interferon signaling, is consistent with previous studies showing caspase-dependent suppression of the cGAS–STING–IFN pathway during DNA virus infection [reviewed in ( 23 )]. A previous study has reported that caspase inhibition also can increase radiation-induced IFN secretion ( 36 ).…”

“…The underlying molecular mechanism of how pan-caspase inhibition increases the IFN response after IR and ATRi remains to be elucidated. Caspases may potentially cleave cGAS or other factors in the cGAS–STING signaling cascade ( 23 , 37 ). Furthermore, the previous study with radiation-induced IFN suggested that caspase inhibition prevents breakdown of irradiated cells with cytosolic DNA ( 36 ).…”

“…Noteworthy, the cGAS–STING–IFN pathway is negatively regulated by three-prime repair exonuclease 1 (TREX1), which degrades the DNA substrates of cGAS ( 21 , 22 ). In addition, this pathway can be negatively regulated by caspase-mediated protein cleavage ( 23 ).…”

Infection and immunity: ‘There Are Things Out There You (Don't) Need To Know About’

“…Different immune cell types limit viral proliferation by inducing suicidal apoptotic pathways or by entering lytic cell death and by alerting neighbouring cells to mount pyroptotic responses. Fang and Peng [14] describe in their review how viruses trigger or dampen caspase activation and how this affects innate immune responses to viral infection. Extensive innate immune signalling and inflammation can undermine protective responses during infection and tissue injury, in particular, when they are not terminated accurately.…”

The Improvement of Sepsis-Associated Encephalopathy by P2X7R Inhibitor through Inhibiting the Omi/HtrA2 Apoptotic Signaling Pathway

“…However, when the body is subjected to severe damaging stimuli, such as the disturbance of the body's internal environment caused by inflammation or biochemical stimulation, the cells of the body will undergo apoptosis caused by aspartate-specific cysteine proteases known as caspases. Cell apoptosis is closely related to mitochondria besides some signaling pathways in the cytoplasm [ 20 ]. Apoptosis caused by mitochondrial pathway is mainly related to the mitochondrial serine protease Omi/HtrA2, which exists in the inner and outer membrane of mitochondria under physiological conditions and is mainly involved in clarifying misfolded proteins in mitochondria [ 21 , 22 ].…”