Human NLRP1 is a sensor for double-stranded RNA
Human NLRP1 is a sensor for double-stranded RNA
复制标题
DOI：
10.1126/science.abd0811
复制
发表时间：
2021-01-29
期刊：
影响因子：
56.9
通讯作者：
Hornung, Veit
中科院分区：
文献类型：
--
作者：
Bauernfried, Stefan;Scherr, Matthias J.;Hornung, Veit
炎性小体作为病原体感染或细胞扰动的细胞内传感器，因此在许多疾病中发挥核心作用。考虑到上皮屏障组织中NLRP1的高丰度，我们筛选了一组不同的病毒来激活角质形成细胞中的炎性体。我们发现塞姆利基森林病毒（SFV）是一种正链RNA病毒，是人类而不是小鼠NLRP1B的有效激活剂。SFV复制和相关的双链RNA形成是NLRP1炎性体参与的必要条件。此外，传递长dsRNA足以触发激活。生化研究表明NLRP1通过其富含亮氨酸的重复结构域与dsRNA结合，导致其NACHT结构域获得腺苷三磷酸酶活性。总之，这些结果确立了人类NLRP1作为dsRNA和RNA病毒感染的直接传感器。
Inflammasomes function as intracellular sensors of pathogen infection or cellular perturbation and thereby play a central role in numerous diseases. Given the high abundance of NLRP1 in epithelial barrier tissues, we screened a diverse panel of viruses for inflammasome activation in keratinocytes. We identified Semliki Forest virus (SFV), a positive-strand RNA virus, as a potent activator of human but not murine NLRP1B. SFV replication and the associated formation of double-stranded (ds) RNA was required to engage the NLRP1 inflammasome. Moreover, delivery of long dsRNA was sufficient to trigger activation. Biochemical studies revealed that NLRP1 binds dsRNA through its leucine-rich repeat domain, resulting in its NACHT domain gaining adenosine triphosphatase activity. Altogether, these results establish human NLRP1 as a direct sensor for dsRNA and thus RNA virus infection.