Viruses (Jan 2023)

Differential Susceptibility of Fetal Retinal Pigment Epithelial Cells, hiPSC- Retinal Stem Cells, and Retinal Organoids to Zika Virus Infection

  • Deisy Contreras,
  • Gustavo Garcia,
  • Melissa Kaye Jones,
  • Laura E. Martinez,
  • Akshaya Jayakarunakaran,
  • Vineela Gangalapudi,
  • Jie Tang,
  • Ying Wu,
  • Jiagang J. Zhao,
  • Zhaohui Chen,
  • Arunachalam Ramaiah,
  • Irena Tsui,
  • Ashok Kumar,
  • Karin Nielsen-Saines,
  • Shaomei Wang,
  • Vaithilingaraja Arumugaswami

DOI
https://doi.org/10.3390/v15010142
Journal volume & issue
Vol. 15, no. 1
p. 142

Abstract

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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.

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