Zika virus-induces metabolic alterations in fetal neuronal progenitors that could influence in neurodevelopment during early pregnancy

Biol Open. 2023 Apr 15;12(4):bio059889. doi: 10.1242/bio.059889. Epub 2023 Apr 21.


Cortical development consists of an orchestrated process in which progenitor cells exhibit distinct fate restrictions regulated by time-dependent activation of energetic pathways. Thus, the hijacking of cellular metabolism by Zika virus (ZIKV) to support its replication may contribute to damage in the developing fetal brain. Here, we showed that ZIKV replicates differently in two glycolytically distinct pools of cortical progenitors derived from human induced pluripotent stem cells (hiPSCs), which resemble the metabolic patterns of quiescence (early hi-NPCs) and immature brain cells (late hi-NPCs) in the forebrain. This differential replication alters the transcription of metabolic genes in both pools of cortical progenitors but solely upregulates the glycolytic capacity of early hi-NPCs. Analysis using Imagestream® revealed that, during early stages of ZIKV replication, in early hi-NPCs there is an increase in lipid droplet abundance and size. This stage of ZIKV replication significantly reduced the mitochondrial distribution in both early and late hi-NPCs. During later stages of ZIKV replication, late hi-NPCs show reduced mitochondrial size and abundance. The finding that there are alterations of cellular metabolism during ZIKV infection which are specific to pools of cortical progenitors at different stages of maturation may help to explain the differences in brain damage over each trimester.

Keywords: Fetal neurodevelopment; Metabolism; Neurometabolism; Neuronal progenitors; ZIKV; Zika virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / metabolism
  • Female
  • Humans
  • Induced Pluripotent Stem Cells* / metabolism
  • Neural Stem Cells* / metabolism
  • Pregnancy
  • Zika Virus Infection*
  • Zika Virus* / metabolism