Inflammasome control of viral infection

Abstract

The inflammasome is a caspase-1 containing complex that activates the proinflammatory cytokines IL-1β and IL-18 and results in the proinflammatory cell death known as pyroptosis. Numerous recent publications have highlighted the importance of inflammasome activation in the control of virus infection. Inflammasome activation during viral infection is dependent on a variety of upstream receptors including the NOD-like receptor, RIG-I-like receptor and AIM2-like receptor families. Various receptors also function in inflammasome activation in different cellular compartments, including the cytoplasm and the nucleus. The effectiveness of inflammasomes at suppressing virus replication is highlighted by the prevalence and diversity of virus encoded inflammasome inhibitors. Also, the host has a myriad of regulatory mechanisms in place to prevent unwanted inflammasome activation and overt inflammation. Finally, recent reports begin to suggest that inflammasome activation and inflammasome modulation may have important clinical applications. Herein, we highlight recent advances and discuss potential future directions toward understanding the role of inflammasomes during virus infection.

Figure 1. ALR signaling pathways

AIM2-like receptors (ALRs) have roles in both inflammasome and inflammasome-independent signaling during virus infection. (1) In particular, IFI16 regulates interferon responses through the adaptor STING, which translocates from the endoplasmic reticulum (ER) to the cytosol in response to IFI16 activation. In the nucleus, IFI16 can bind viral DNA (vDNA) and activate the inflammasome in the nucleus (2) or peri-nuclear space (3). (4) IFI16 appears to both positively and negatively regulate gene expression through DNA binding and affecting histone modifications and chromatin packaging. (5) In the cytosol, AIM2 can recognize DNA of cellular or pathogen origin and activate the inflammasome. The only requirement for AIM2 recognition of DNA appears to be cytosolic localization. However, IFI16 binding of different forms of DNA must affect the function of IFI16 in an undefined fashion.