Herpesviruses and Inflammasomes: One Sensor Does Not Fit All

Abstract

Herpesviruses are ubiquitous double-stranded DNA viruses that cause lifelong infections and are associated with a variety of diseases. While they have evolved multiple mechanisms to evade the immune system, they are all recognized by the innate immune system, which can lead to both localized and systemic inflammation. A more recently appreciated mechanism of herpesvirus innate immune activation is through inflammasome signaling. The inflammasome is an intracellular multiprotein complex that, when activated, leads to the release of proinflammatory cytokines, including IL-1b and IL-18, and activation of the inflammatory programed cell death pathway known as pyroptosis. Despite the herpesviruses sharing a similar structure, their mechanisms of inflammasome activation and the consequences of inflammasome activation in cases of virus-associated disease are not uniform. This review will highlight the similarities and differences among herpesviruses with regard to their mechanisms of inflammasome activation and impacts on diseases caused by herpesviruses. Furthermore, it will identify areas where additional studies are warranted to better understand the impact of this important innate immune signaling program on the pathogenesis of these common viruses.