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

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.

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    State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China. Institute of Medical Microbiology, Jinan University, Guangzhou, 510632, P.R. China.

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    School of Chinese Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, 510006, P.R. China.

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    Institute of Pathogenic Microbiology, Center for Disease Control and Prevention of Guangdong, Guangzhou, 510006, P.R. China.

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    Institute of Medical Microbiology, Jinan University, Guangzhou, 510632, P.R. China.

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    State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China.

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    State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China.

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    State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China.

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    State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China.

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    State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China.

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    State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China.

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    School of Chinese Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, 510006, P.R. China.

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    School of Physics and Technology, Wuhan University, Wuhan, 430072, P.R. China.

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    State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China. liufung@whu.edu.cn.

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    State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China. mvlwu@whu.edu.cn. Institute of Medical Microbiology, Jinan University, Guangzhou, 510632, P.R. China. mvlwu@whu.edu.cn.

    State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China. jwu@whu.edu.cn. Institute of Medical Microbiology, Jinan University, Guangzhou, 510632, P.R. China. jwu@whu.edu.cn.

    Source

    Nature communications 9:1 2018 Jan 09 pg 106

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    29317641