Activation of Interleukin-1β Release by the Classical Swine Fever Virus Is Dependent on the NLRP3 Inflammasome, Which Affects Virus Growth in Monocytes.

Activation of Interleukin-1β Release by the Classical Swine Fever Virus Is Dependent on the NLRP3 Inflammasome, Which Affects Virus Growth in Monocytes.
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猪瘟病毒激活白细胞介素 1 β 的释放依赖于 NLRP3 炎症小体,这会影响单核细胞中的病毒生长

DOI:
10.3389/fcimb.2018.00225
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发表时间:
2018
影响因子:
5.7
通讯作者:
Zhao M
Zhao M
中科院分区:
医学2区
文献类型:
--
作者:
Fan S;Yuan J;Deng S;Chen Y;Xie B;Wu K;Zhu M;Xu H;Huang Y;Yang J;Zhang Y;Chen J;Zhao M

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猪瘟病毒 (CSFV) 是一种典型的黄病毒,可引起急性、发热和高度传染性疾病,称为猪瘟 (CSF)。炎症小体是触发促炎细胞因子成熟以参与细胞感染或应激时诱导的先天免疫防御的分子平台。然而,炎症小体与猪瘟病毒感染之间的关系尚未得到彻底的表征。为了了解炎症小体对 CSFV 感染的反应功能,我们用 CSFV 感染猪外周血单核细胞 (PBMC)。我们的结果表明,CSFV感染诱导了白细胞介素原1β(pro-IL-1β)的产生及其在单核细胞中的加工,通过激活caspase 1导致IL-1β的成熟和分泌。此外,PBMC中的CSFV感染诱导了gasdermin D(GSDMD)的产生和裂解,这是细胞焦亡的诱导剂。其他研究表明,CSFV 诱导的 IL-1β 分泌是由 NLRP3 介导的,并且 CSFV 感染可以充分激活单核细胞中 NLRP3 炎性小体的组装。这些结果表明,CSFV感染抑制了NLRP3的表达,并且NLRP3的敲低增强了CSFV的复制。总之,这些发现表明 NLRP3 炎性体在针对 CSFV 感染的先天免疫反应中发挥重要作用。
Classical swine fever virus (CSFV) is a classic Flavivirus that causes the acute, febrile, and highly contagious disease known as classical swine fever (CSF). Inflammasomes are molecular platforms that trigger the maturation of proinflammatory cytokines to engage innate immune defenses that are induced upon cellular infection or stress. However, the relationship between the inflammasome and CSFV infection has not been thoroughly characterized. To understand the function of the inflammasome response to CSFV infection, we infected porcine peripheral blood monocytes (PBMCs) with CSFV. Our results indicated that CSFV infection induced both the generation of pro-interleukin-1β (pro-IL-1β) and its processing in monocytes, leading to the maturation and secretion of IL-1β through the activation of caspase 1. Moreover, CSFV infection in PBMCs induced the production and cleavage of gasdermin D (GSDMD), which is an inducer of pyroptosis. Additional studies showed that CSFV-induced IL-1β secretion was mediated by NLRP3 and that CSFV infection could sufficiently activate the assembly of the NLRP3 inflammasome in monocytes. These results revealed that CSFV infection inhibited the expression of NLRP3, and knockdown of NLRP3 enhanced the replication of CSFV. In conclusion, these findings demonstrate that the NLRP3 inflammasome plays an important role in the innate immune response to CSFV infection.
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