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Mosquito- and tick-borne orthoflavivirus infections dysregulate microcephaly-associated genes in human neural progenitor cells

ABSTRACT: Human neural progenitor cell (hNPC) transcriptomic responses to infections with Zika virus (ZIKV), Powassan virus (POWV), or two strains of West Nile virus were analyzed at three times after infection in a single batch of hNPCs differentiated from induced pluripotent stem cells. The WNV infections displayed the fastest replication kinetics but the POWV infection produced the highest viral yield. All four infections upregulated common and unique innate immune and antiviral response genes by 12 hpi and induced upregulation of stress pathway genes by 24 hpi. The WNV infections downregulated cell cycle genes earlier than the ZIKV or POWV infections. Transcription factors regulating gene expression changes were predicted. All four orthoflaviviruses dysregulated the expression of 262 microcephaly-associated genes, with virus-specific differences in the extent of dysregulation. The data suggest that fetal hNPC infection in utero by each of the four orthoflaviviruses studied could induce neurodevelopmental disorders.

ORGANISM(S): Homo sapiens

PROVIDER: GSE309623 | GEO | 2026/04/02

REPOSITORIES: GEO

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