Talk title Hitting two birds with one stone: Zika virus NS5 protein suppresses antiviral response but activates gamma interferon signaling
Speaker Prof. Dong-Yan JIN
Clara and Lawrence Fok Professor in Precision Medicine, The University of Hong Kong (HKU)
Date & Time 8 May 2018 (Tuesday) 15:00-16:00
Venue Room G003, E12 Building (University of Macau)
Abstract Inflammation might be the cause of severe complications of Zika virus (ZIKV) infection. It is not known how ZIKV fuels inflammation in infected tissues. We demonstrate that ZIKV uses its NS5 protein to suppress innate antiviral response mediated by type I and type III interferons (IFNs) but activate type II IFN signaling. Treatment of infected cells with IFN-γ boosted ZIKV replication. ZIKV NS5 interacted with STAT2 and promoted its degradation. As a result, the formation of STAT1-STAT2-IRF9 and its occupancy of IFN-β-stimulated genes was reduced. On the contrary, the assembly of STAT1-STAT1 and its occupancy of IFN-γ-stimulated genes was enhanced. Notably, inhibition of IFN-γ signaling suppressed viral replication and inflammation. Whereas ZIKV replication in cultured cells was boosted by IFN-γ-stimulated proinflammatory cytokine CXCL10, induction of PD-L1 and activation of immune checkpoint were observed in mouse model of ZIKV infection. Augmentation of ZIKV replication in vivo was plausibly mediated by suppression of T cell response. Our work suggests that ZIKV NS5 protein differentially modulates IFN signaling to boost viral replication and cause inflammation. This ability might be shared by several pathogenic viruses.