1. Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS1-caspase-1 axis.
- Author
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Zheng Y, Liu Q, Wu Y, Ma L, Zhang Z, Liu T, Jin S, She Y, Li YP, and Cui J
- Subjects
- Animals, Caspase 1 genetics, Chlorocebus aethiops, Endopeptidases genetics, Endopeptidases immunology, Endosomal Sorting Complexes Required for Transport genetics, Endosomal Sorting Complexes Required for Transport immunology, HEK293 Cells, Humans, Inflammasomes genetics, Inflammasomes immunology, Inflammation genetics, Inflammation immunology, Inflammation pathology, Inflammation virology, Mice, Mice, Knockout, Nucleotidyltransferases genetics, Signal Transduction genetics, THP-1 Cells, Ubiquitin Thiolesterase genetics, Ubiquitin Thiolesterase immunology, Vero Cells, Viral Nonstructural Proteins genetics, Zika Virus genetics, Caspase 1 immunology, Immune Evasion, Nucleotidyltransferases immunology, Proteolysis, Signal Transduction immunology, Viral Nonstructural Proteins immunology, Zika Virus immunology
- 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 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., (© 2018 The Authors.)
- Published
- 2018
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