Nonstructural protein NSs activates inflammasome and pyroptosis through interaction with NLRP3 in human microglial cells infected with severe fever with thrombocytopenia syndrome Bandavirus

Severe fever with thrombocytopenia syndrome virus (SFTSV) infection causes neurological disorders in humans. In this report, it was shown that SFTSV can infect microglial cells in the brain of neonatal BALB/c mice. This infection stimulated interleukin-1b (IL-1b) secretion in the brain. The secretion of IL-1b was induced by NLRP3 inflammasome activation, which was shown to be stimulated by viral NSs protein via a protein-protein interaction. Knockdown of NLRP3 or inhibition of inflammasome activation suppressed viral replication, suggesting that the activation of NLRP3 inflammasome supports SFTSV replication in microglial cells. This activation of microglial cells may lead to the neural cell death and inflammation that are associated with neurological disorders.