Zika Virus Elicits Inflammation to Evade Antiviral Response by Cleaving CGAS Via NS1-caspase-1 Axis

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2018 Aug 2

PMID 30065070

Citations 116

Authors

Yanyan Zheng

Qingxiang Liu

Yaoxing Wu

Ling Ma

Zhenzhen Zhang

Tao Liu

Shouheng Jin

Yuanchu She

Yi-Ping Li

Jun Cui

Affiliations

Soon will be listed here.

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 and 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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