White spot syndrome virus infection induces Caspase 1-mediated antiviral cell death in crustacean

In vertebrates, pyroptosis is an intensely inflammatory form of programmed cell death which is dependent on Caspase 1 activation and release of cytoplasmic cytokines including IL-1β. This death pathway is critical for controlling pathogenic infection by mobilizing immune cells and stimulating the development of adaptive immune response. In invertebrates, however, due to the lack of adaptive immune response, it is still elusive whether Caspase 1-dependent cell death pathway exists. In this study, our data showed that Caspase 1-mediated cell death was activated by white spot syndrome virus (WSSV) infection to control the virus in shrimp. Caspase 1 had a higher expression level in hemocytes and lymphoid-like organ in shrimp and WSSV infection was significantly promoted upon the inhibition of Caspase 1 enzymatic activity. IL-1β-like protein was identified as the substrate of Caspase 1 and its interaction with Caspase 1 was validated ectopically and endogenously. Moreover, IL-1β like protein was released into extracellular contents under WSSV infection and Prophenoloxidase system was activated, resulting in the reduction of WSSV copies in vivo. Our data unraveled a previously unidentified mechanism through which Caspase 1-dependent cell death controlled virus infection in shrimp. Therefore, our study opened the possibility that an invertebrate cytokine network might be operative and regulate host defenses against virus infection as in vertebrates.