Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS1‐caspase‐1 axis |
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| Authors: | Ling Ma Zhenzhen Zhang Tao Liu Shouheng Jin Yuanchu She Yi‐Ping Li Jun Cui |
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| Affiliation: | 1. Institute of Human Virology, Key Laboratory of Tropical Diseases Control Ministry of Education, Zhongshan School of Medicine, Sun Yat‐sen University, Guangzhou, China;2. MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat‐sen University, Guangzhou, Guangdong, China;3. Department of Infectious Disease, The Fifth Affiliated Hospital of Sun Yat‐sen University, Zhuhai, China |
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| Abstract: | Viral infection triggers host innate immune responses, which primarily include the activation of type I interferon (IFN) signaling and inflammasomes. Here, we report that Zika virus (ZIKV) infection triggers NLRP3 inflammasome activation, which is further enhanced by viral non‐structural protein NS1 to benefit its replication. NS1 recruits the host deubiquitinase USP8 to cleave K11‐linked poly‐ubiquitin chains from caspase‐1 at Lys134, thus inhibiting the proteasomal degradation of caspase‐1. The enhanced stabilization of caspase‐1 by NS1 promotes the cleavage of cGAS, which recognizes mitochondrial DNA release and initiates type I IFN signaling during ZIKV infection. NLRP3 deficiency increases type I IFN production and strengthens host resistance to ZIKVin vitro and in vivo. Taken together, our work unravels a novel antagonistic mechanism employed by ZIKV to suppress host immune response by manipulating the interplay between inflammasome and type I IFN signaling, which might guide the rational design of therapeutics in the future. |
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| Keywords: | antiviral immunity inflammasome type I interferon signaling Zika virus |
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