Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS1-caspase-1 axis

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.

Source: EMBO Journal - September 14, 2018 Category: Molecular Biology Authors: Zheng, Y., Liu, Q., Wu, Y., Ma, L., Zhang, Z., Liu, T., Jin, S., She, Y., Li, Y.-P., Cui, J. Tags: Immunology, Microbiology, Virology & Host Pathogen Interaction Articles Source Type: research