Zika virus infection induces host inflammatory responses by facilitating NLRP3 inflammasome assembly and interleukin-1\u03b2 secretion

Wenbiao Wang,Zhen Luo,Jianguo Wu,Kailang Wu,Yingchong Wang,Lang Rao,Xiaohong Liu,Aixin Li,Mingfu Tian,Pan Pan,Geng Li,Feng Xiao,De Wu De Wu,Yingle Liu,Fang Liu

doi:10.1038/s41467-017-02645-3

Wenbiao Wang, Zhen Luo + Show 13 more

Open Access

https://doi.org/10.1038/s41467-017-02645-3

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Abstract

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.

Highlights

Zika virus (ZIKV) infection is a public health emergency and host innate immunity is essential for the control of virus infection
We initially showed that IL-1β levels in the sera of ZIKV-infected patients (n = 11) were higher than those in healthy individuals (n = 13) (Fig. 1a), suggesting that ZIKV infection is associated with IL-1β secretion
In phorbol-12-myristate-13-acetate (TPA)-differentiated THP-1 macrophages[26], IL-1β mRNA was activated by ZIKV but not by Nigericin (Fig. 1h, j), IL-1β secretion was induced by Nigericin and ZIKV (Fig. 1I, k), IL-1β maturation and Casp-1 cleavage in cell supernatants, and pro-IL-1β production in cell lysates were activated by Nigericin and ZIKV (Fig. 1l, m)

Summary

Introduction

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. ZIKV NS5 protein is required for NLRP3 activation and IL-1β secretion by binding with NLRP3 to facilitate the inflammasome complex assembly. We reveal a mechanism by which ZIKV induces inflammatory responses by facilitating NLRP3 inflammasome complex assembly and IL-1β activation. The NLRs are involved in the assembly of large protein complexes known as inflammasomes, which are involved in the innate immune response to pathogens[19]. We reveal a mechanism by which ZIKV infection induces host inflammatory responses by facilitating the NLRP3 inflammasome assembly and IL-1β secretion. We report a function of ZIKV NS5 in regulating the NLRP3 inflammasome and reveal a mechanism by which ZIKV induces host inflammatory and immune responses

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