Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth

• Authors: Hengli Tang, Florida State University; Christy Hammack, Florida State University; Sarah C. Ogden, Florida State University; Zhexing Wen, Emory University; Xuyu Qian, Johns Hopkins University; Yujing Li, Emory University; Bing Yao, Emory University; Jaehoon Shin, Johns Hopkins University; Feiran Zhang, Emory University; Emily M. Lee, Florida State University; Kimberly M. Christian, Johns Hopkins University; Ruth A. Didier, Florida State University; Peng Jin, Emory University; Hongjun Song, Johns Hopkins University; Guo-Li Ming, Johns Hopkins University
• Journal Title: Cell Stem Cell
• Volume: Volume 18, Number 5
• Publisher: Elsevier (Cell Press) | 2016-05-05, Pages 587-590
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.stem.2016.02.016
• Subjects: Biology, Neuroscience; Biology, Cell
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cell & Tissue Engineering; Cell Biology; CELLS

Abstract

The suspected link between infection by Zika virus (ZIKV), a re-emerging flavivirus, and microcephaly is an urgent global health concern. The direct target cells of ZIKV in the developing human fetus are not clear. Here we show that a strain of the ZIKV, MR766, serially passaged in monkey and mosquito cells efficiently infects human neural progenitor cells (hNPCs) derived from induced pluripotent stem cells. Infected hNPCs further release infectious ZIKV particles. Importantly, ZIKV infection increases cell death and dysregulates cell-cycle progression, resulting in attenuated hNPC growth. Global gene expression analysis of infected hNPCs reveals transcriptional dysregulation, notably of cell-cycle-related pathways. Our results identify hNPCs as a direct ZIKV target. In addition, we establish a tractable experimental model system to investigate the impact and mechanism of ZIKV on human brain development and provide a platform to screen therapeutic compounds.