NLRs, inflammasomes, and viral infection

Abstract

NLR proteins are innate immune sensors that respond to microbial infection. Upon pathogen infection, some NLR proteins form large complexes, called inflammasomes, which activate caspase-1 and induce the production of active IL-1β and IL-18. Activation of inflammasomes can also lead to an inflammatory cell death program, named pyroptosis. In this review, we will discuss the role of various NLR proteins in sensing different viral infections, as well as the strategies used by several RNA and DNA viruses to counteract the antiviral effects of NLR-dependent inflammasomes.

Figure 1.. Viral proteins inhibit various steps of the NLR-dependent inflammasome pathway.

Some poxviruses encode scavenger receptors (vIL-1βR) and IL-18BPs, which compete with IL-1β and IL-18 from binding their cognate receptors. Moreover, MxV and Shope fibroma virus encode vPOPs, which bind ASC to prevent inflammasome formation through caspase-1 recruitment. Measles virus encodes a nonstructural V protein that interacts with and inhibits NLRP3. Similarly, KSHV encodes the Orf63 protein, which shows similarity to cellular NLRP1 and can interact with cellular NLRP1 and NLRP3 to prevent the formation of inflammasomes. Poxvirus family members encode serpins such as CrmA, SP1/2 (SPI-1/2), and Serp2, which inhibit caspase-1 activity and prevent IL-1β and IL-18 secretion. The NS1 protein of influenza also inhibits caspase-1, IL-1β, and IL-18 activation and secretion. HMGB1, High mobility group box 1.