Abstract：
Lyssavirus is a kind of neurotropic pathogen that needs to evade peripheral host immunity to enter the central nervous system to accomplish infection. NLRP3 inflammasome activation is essential for the host to defend against pathogen invasion. This study demonstrates that the matrix protein (M) of lyssavirus can inhibit both the priming step and the activation step of NLRP3 inflammasome activation. Specifically, M of lyssavirus can compete with NEK7 for binding to NLRP3, which restricts downstream apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization. The serine amino acid at the 158th site of M among lyssavirus is critical for restricting ASC oligomerization. Moreover, recombinant lab-attenuated lyssavirus rabies (rabies lyssavirus [RABV]) with G158S mutation at M decreases interleukin-1β (IL-1β) production in bone-marrow-derived dendritic cells (BMDCs) to facilitate lyssavirus invasion into the brain thereby elevating pathogenicity in mice. Taken together, this study reveals a common mechanism by which lyssavirus inhibits NLRP3 inflammasome activation to evade host defenses.
摘要：
镰刀病毒是一种嗜神经病原体，需要逃避外周宿主免疫进入中枢神经系统来完成感染。NLRP3炎性体激活对于宿主防御病原体入侵至关重要。这项研究表明，裂解病毒的基质蛋白（M）可以抑制NLRP3炎性体激活的引发步骤和激活步骤。具体来说,M的裂解病毒可以与NEK7竞争结合NLRP3，这限制了下游凋亡相关的斑点样蛋白，其中含有CARD（ASC）寡聚化。Lyssavirus中M的第158位的丝氨酸氨基酸对于限制ASC寡聚化至关重要。此外，在M处具有G158S突变的重组实验室减毒狂犬病病毒（狂犬病狂犬病病毒[RABV]）可降低骨髓来源的树突状细胞（BMDCs）中白介素1β（IL-1β）的产生，以促进狂犬病病毒侵入大脑，从而提高小鼠的致病性。一起来看,这项研究揭示了一种常见的机制，通过该机制，lyssavirus抑制NLRP3炎性体激活，以逃避宿主防御。
