Biology Open · 4 authors, 3 centres
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This preclinical study used human induced pluripotent stem cell-derived cortical progenitors (hi-NPCs) to model fetal brain development and found that Zika virus infection causes differential metabolic changes and cell death depending on the progenitors' maturation stage, with less mature, early-stage cells being more vulnerable.
Researchers cultured hiPSC-derived cortical progenitors (hi-NPCs) and characterized two pools of cells at distinct differentiation timepoints, termed 'early' and 'late' hi-NPCs. Metabolic tracing revealed that early hi-NPCs exhibited high glycolytic flux and low fatty acid oxidation, while late hi-NPCs showed the opposite, indicating a shift towards mitochondrial metabolism consistent with advancing maturation. Infection with a low-passage African ZIKV strain demonstrated that early hi-NPCs experienced significantly higher cell death and increased glucose consumption at later replication stages compared to late hi-NPCs. Conversely, late hi-NPCs accumulated more viral transcripts and released more virions. Transcriptional analysis showed ZIKV infection upregulated glycolytic genes in both cell pools. The findings suggest ZIKV-induced metabolic disruptions are stage-dependent, potentially explaining the higher risk of severe neurodevelopmental consequences from infection during the first trimester.
