mSphere 2021 Jun 9:e0036121. Epub 2021 Jun 9.
Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, Manchester, United Kingdom.
To study how the Zika virus (ZIKV) interacts with the host unfolded protein response (UPR), we undertook a kinetics study. We show that ZIKV infection triggers an atypical tripartite UPR in A549 cells involving transient activation of the effectors X-box-binding protein 1, activating transcription factor 4 (ATF4), CCAAT enhancer-binding protein-homologous protein, and growth arrest and DNA damage-inducible protein 34 during early infection and sustained activation of all three UPR sensors: RNA-activated protein kinase-like endoplasmic reticulum-resident kinase (PERK), inositol-requiring kinase-1α (IRE1α), and ATF6. Sustained phosphorylation of the eukaryotic translation initiation factor 2α and rRNA degradation coincide with host translational shutoff, cell lysis, and virus release during late infection. Read More