PT - JOURNAL ARTICLE AU - Deisy Contreras AU - Melissa Kaye Jones AU - Laura E. Martinez AU - Vineela Gangalapudi AU - Jie Tang AU - Ying Wu AU - Jiagang J. Zhao AU - Zhaohui Chen AU - Shaomei Wang AU - Vaithilingaraja Arumugaswami TI - Modeling Zika Virus Congenital Eye Disease: Differential Susceptibility of Fetal Retinal Progenitor Cells and iPSC-Derived Retinal Stem Cells to Zika Virus Infection AID - 10.1101/128405 DP - 2017 Jan 01 TA - bioRxiv PG - 128405 4099 - http://biorxiv.org/content/early/2017/04/18/128405.short 4100 - http://biorxiv.org/content/early/2017/04/18/128405.full AB - Zika virus (ZIKV) causes microcephaly and congenital eye disease that is characterized by macular pigment mottling, macular atrophy, and loss of foveal reflex. The cell and molecular basis of congenital ZIKV infection are not well understood. Here, we utilized a biologically relevant cell-based system on human fetal retinal pigment epithelial cells (FRPE) and iPSC-derived retinal stem cells (iRSCs) to model ZIKV-ocular cell injury processes. FRPEs were highly susceptible to ZIKV, resulting in apoptosis and decreased viability, whereas iRSCs showed reduced susceptibility. Transcriptomics and proteomics analyses of infected FRPE cells revealed the activation of innate immune and inflammatory response genes, and dysregulation of cell survival pathways, mitochondrial transmembrane potential, phagocytosis, and particle internalization. Nucleoside analogue drug treatment inhibited ZIKV replication and prevented apoptosis. In conclusion, ZIKV affects ocular cells of different developmental stages resulting in cellular injury and death, further providing molecular insight into the pathogenesis of congenital eye disease.