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Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS 1‐caspase‐1 axis
Author(s) -
Zheng Yanyan,
Liu Qingxiang,
Wu Yaoxing,
Ma Ling,
Zhang Zhenzhen,
Liu Tao,
Jin Shouheng,
She Yuanchu,
Li YiPing,
Cui Jun
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201899347
Subject(s) - biology , inflammation , zika virus , virology , virus , viral replication , microbiology and biotechnology , immunology
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 NLRP 3 inflammasome activation, which is further enhanced by viral non‐structural protein NS 1 to benefit its replication. NS 1 recruits the host deubiquitinase USP 8 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 NS 1 promotes the cleavage of cGAS , which recognizes mitochondrial DNA release and initiates type I IFN signaling during ZIKV infection. NLRP 3 deficiency increases type I IFN production and strengthens host resistance to ZIKV in 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.