NLRP3 Inflammasome Activation Mediates Zika Virus-Associated Inflammation
NLRP3 Inflammasome Activation Mediates Zika Virus-Associated Inflammation
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NLRP3 炎症小体激活介导寨卡病毒相关炎症
DOI：
10.1093/infdis/jiy129
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发表时间：
2018-06-15
影响因子：
6.4
通讯作者：
Li, Mengfeng
中科院分区：
文献类型：
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作者：
He, Zhenjian;Chen, Jiahui;Li, Mengfeng
寨卡病毒（ZIKV）是一种蚊媒病毒，已被确定为几种严重疾病表现的原因，包括先天性小头畸形和格林-巴利综合征、脑膜脑炎和肌萎缩症。先前的研究表明，ZIKV感染的患者表现出升高的血浆白细胞介素1 β（IL-1 β）水平，表明ZIKV可能激活炎性小体。然而，其病毒发病机制的分子基础仍然知之甚少。在目前的研究中，我们发现ZIKV感染引起严重的炎症病理变化，并在体外和体内促进IL-1 β的产生。我们在此证明，ZIKV感染期间IL-1 β的成熟和分泌由NLRP 3炎性小体活化介导，并且ZIKV非结构蛋白5（NS5）促进NLRP 3炎性小体复合物的组装，通过与NLRP 3相互作用和诱导活性氧产生而导致IL-1 β活化。总的来说，我们的数据将NLRP 3炎性体衍生的IL-1 β产生鉴定为ZIKV感染期间炎症的关键特征。这些发现为炎性小体介导的疾病提供了新的见解，并可能为ZIKV相关疾病提供新的治疗选择。
Zika virus (ZIKV) is a mosquito-borne virus that has been identified as a cause of several severe disease manifestations, including congenital microcephaly and Guillain-Barre syndrome, meningoencephalitis, and myelitis. Previous studies showed that ZIKVinfected patients exhibited elevated plasma levels of interleukin 1 beta (IL-1 beta), indicating that ZIKV may activate inflammasomes. However, the molecular basis for its viral pathogenesis remains poorly understood. In this current study, we found that ZIKV infection caused severe inflammatory pathological changes and promoted IL-1 beta production in vitro and in vivo. We here demonstrate that the maturation and secretion of IL-1 beta during ZIKV infection was mediated by NLRP3 inflammasome activation and that ZIKV nonstructural protein 5 (NS5) facilitated the assembly of the NLRP3 inflammasome complex, leading to IL-1 beta activation through interaction with NLRP3 and induction of reactive oxygen species production. Collectively, our data identify NLRP3 inflammasomederived IL-1 beta production as a critical feature of inflammation during ZIKV infection. These findings offer new insights into inflammasome-mediated diseases and may provide new therapeutic options for ZIKV-associated diseases.