Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Viruses. 2023 Jan 1;15(1):142. doi: 10.3390/v15010142.
Zika virus (ZIKV) causes microcephaly and congenital eye disease. The cellular and molecular basis of congenital ZIKV infection are not well understood. Here, we utilized a biologically relevant cell-based system of human fetal retinal pigment epithelial cells (FRPEs), hiPSC-derived retinal stem cells (iRSCs), and retinal organoids to investigate ZIKV-mediated ocular cell injury processes. Our data show that FRPEs were highly susceptible to ZIKV infection exhibiting increased apoptosis, whereas iRSCs showed reduced susceptibility. Detailed transcriptomics and proteomics analyses of infected FRPEs were performed. Nucleoside analogue drug treatment inhibited ZIKV replication. Retinal organoids were susceptible to ZIKV infection. The Asian genotype ZIKV exhibited higher infectivity, induced profound inflammatory response, and dysregulated transcription factors involved in retinal organoid differentiation. Collectively, our study shows that ZIKV affects ocular cells at different developmental stages resulting in cellular injury and death, further providing molecular insight into the pathogenesis of congenital eye disease.
寨卡病毒（ZIKV）可导致小头畸形和先天性眼部疾病。先天性 ZIKV 感染的细胞和分子基础尚不清楚。在这里，我们利用一种具有生物学相关性的人胎儿视网膜色素上皮细胞（FRPE）、iPSC 衍生的视网膜干细胞（iRSCs）和视网膜类器官的细胞培养系统，研究 ZIKV 介导的眼部细胞损伤过程。我们的数据表明，FRPEs 极易受到 ZIKV 感染，表现出细胞凋亡增加，而 iRSCs 则表现出较低的易感性。对感染的 FRPEs 进行了详细的转录组学和蛋白质组学分析。核苷类似物药物治疗抑制了 ZIKV 的复制。视网膜类器官易受 ZIKV 感染。亚洲基因型 ZIKV 表现出更高的感染力，引起了严重的炎症反应，并使参与视网膜类器官分化的转录因子失调。总的来说，我们的研究表明，ZIKV 可影响不同发育阶段的眼部细胞，导致细胞损伤和死亡，从而为先天性眼部疾病的发病机制提供了分子见解。
