Role of ASC in West Nile Virus Encephalitis

The inflammasome adaptor protein, apoptosis-associated speck-like protein containing CARD (ASC), mediates a critical step in innate immune signaling by bridging the interaction between the NLRPs and caspase-1 in inflammasome complexes. In this study, we demonstrated that ASC is essential for the activation of caspase-1 and IL-1beta production. ASC-/- mice exhibited increased susceptibility to West Nile virus (WNV), and reduced survival was associated with enhanced virus replication in the CNS. Infected ASC-/- mice also displayed reduced levels of cytokines, IFN-alpha and IgM in serum. However, brains from ASC-/- mice displayed elevated levels of pro-inflammatory cytokines, which correlated with more pronounced activation of astrocytes, enhanced infiltration of peripheral immune cells in the CNS and increased neuronal cell death. Collectively, our data provides new insights into the role of ASC as an essential modulator of inflammasome-dependent and -independent immune response to effectively control WNV infection.

Kumar M, Roe K, Orillo B, Muruve DA, Nerurkar VR, Gale M, Verma S. (2013) Inflammasome adaptor protein apoptosis-associated speck-like protein containing CARD (ASC) is critical for the immune response and survival in West Nile virus encephalitis. Journal of Virology 87(7):3655-3667.