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

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

doi:10.1038/s41467-017-02645-3

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

Nat Commun. 2018 Jan 9;9(1):106. doi: 10.1038/s41467-017-02645-3.

Authors

Wenbiao Wang^{1

2}, Geng Li³, De Wu⁴, Zhen Luo², Pan Pan¹, Mingfu Tian¹, Yingchong Wang¹, Feng Xiao¹, Aixin Li¹, Kailang Wu¹, Xiaohong Liu³, Lang Rao⁵, Fang Liu⁶, Yingle Liu^{7

8}, Jianguo Wu^{9

10}

Affiliations

¹ State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China.
² Institute of Medical Microbiology, Jinan University, Guangzhou, 510632, P.R. China.
³ School of Chinese Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, 510006, P.R. China.
⁴ Institute of Pathogenic Microbiology, Center for Disease Control and Prevention of Guangdong, Guangzhou, 510006, P.R. China.
⁵ School of Physics and Technology, Wuhan University, Wuhan, 430072, P.R. China.
⁶ State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China. [email protected].
⁷ State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China. [email protected].
⁸ Institute of Medical Microbiology, Jinan University, Guangzhou, 510632, P.R. China. [email protected].
⁹ State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China. [email protected].
¹⁰ Institute of Medical Microbiology, Jinan University, Guangzhou, 510632, P.R. China. [email protected].

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aedes
Animals
Brain / immunology
Brain / pathology
Caspase 1 / genetics
Caspase 1 / immunology
Cell Line
Chlorocebus aethiops
Enzyme Activation / genetics
Enzyme Activation / immunology
HEK293 Cells
Humans
Immunity, Innate / immunology
Inflammasomes / immunology*
Interleukin-1beta / blood
Interleukin-1beta / metabolism*
Kidney / immunology
Kidney / pathology
L Cells
Liver / immunology
Liver / pathology
Macrophages / immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
NLR Family, Pyrin Domain-Containing 3 Protein / genetics
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
Neutrophils / immunology
Spleen / immunology
Spleen / pathology
THP-1 Cells
Vero Cells
Viral Nonstructural Proteins / immunology
Zika Virus / immunology*
Zika Virus Infection / immunology*
Zika Virus Infection / virology

Substances

Inflammasomes
Interleukin-1beta
NLR Family, Pyrin Domain-Containing 3 Protein
NS5 protein, flavivirus
Nlrp3 protein, mouse
Viral Nonstructural Proteins
Casp1 protein, mouse
Caspase 1