Zika virus infection induces host inflammatory responses by facilitating NLRP3 inflammasome assembly and interleukin-1β secretion.
Wenbiao WangGeng Linull De WuZhen LuoPan PanMingfu TianYingchong WangFeng XiaoAixin LiKailang WuXiaohong LiuLang RaoFang LiuYingle LiuJian-Guo WuPublished in: Nature communications (2018)
Zika virus (ZIKV) infection is a public health emergency and host innate immunity is essential for the control of virus infection. The NLRP3 inflammasome plays a key role in host innate immune responses by activating caspase-1 to facilitate interleukin-1β (IL-1β) secretion. Here we report that ZIKV stimulates IL-1β secretion in infected patients, human PBMCs and macrophages, mice, and mice BMDCs. The knockdown of NLRP3 in cells and knockout of NLRP3 in mice inhibit ZIKV-mediated IL-1β secretion, indicating an essential role for NLRP3 in ZIKV-induced IL-1β activation. Moreover, ZIKV NS5 protein is required for NLRP3 activation and IL-1β secretion by binding with NLRP3 to facilitate the inflammasome complex assembly. Finally, ZIKV infection in mice activates IL-1β secretion, leading to inflammatory responses in the mice brain, spleen, liver, and kidney. Thus we reveal a mechanism by which ZIKV induces inflammatory responses by facilitating NLRP3 inflammasome complex assembly and IL-1β activation.
Keyphrases
- nlrp inflammasome
- zika virus
- dengue virus
- public health
- immune response
- high fat diet induced
- aedes aegypti
- induced apoptosis
- cell death
- emergency department
- signaling pathway
- endothelial cells
- type diabetes
- inflammatory response
- multiple sclerosis
- white matter
- cell proliferation
- protein protein
- stress induced
- diabetic rats
- drug induced