Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection

• Published in: Stem cell reports 2017-03, Vol.8 (3), p.715-727
• Main Authors: McGrath, Erica L., Rossi, Shannan L., Gao, Junling, Widen, Steven G., Grant, Auston C., Dunn, Tiffany J., Azar, Sasha R., Roundy, Christopher M., Xiong, Ying, Prusak, Deborah J., Loucas, Bradford D., Wood, Thomas G., Yu, Yongjia, Fernández-Salas, Ildefonso, Weaver, Scott C., Vasilakis, Nikos, Wu, Ping
• Format: Article
• Language: English
• Subjects: Animals; astrocyte; Astrocytes; Brain - immunology; Brain - metabolism; Brain - virology; Cell Differentiation; Cell Proliferation; Cell Survival; Chlorocebus aethiops; Cluster Analysis; differentiation; Fetus; Gene Expression; Gene Expression Profiling; human neural stem cell; Humans; Immunity, Innate; innate immunity; Male; Mice; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neural Stem Cells - virology; neurogenesis; Neurogenesis - genetics; neuron; Neurons; proliferation; Transcriptome; Vero Cells; Zika virus; Zika Virus - classification; Zika Virus - physiology; Zika Virus Infection - genetics; Zika Virus Infection - immunology; Zika Virus Infection - metabolism; Zika Virus Infection - virology
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2017.01.008

Zika virus (ZIKV) infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7), to infect primary human neural stem cells (hNSCs) originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection. [Display omitted] •Mexican ZIKV strain infects primary human fetal brain-derived neural stem cells•ZIKV inhibits neuronal differentiation in a cell-strain-dependent manner•Majority of differentiated ZIKV-infected cells are glial cells•ZIKV-mediated transcriptome alteration is cell-strain-dependent In this article, Wu, Vasilakis, and colleagues demonstrate the infection of primary human fetal brain-derived neural stem cells by a 2015 Mexican strain of ZIKV. They show that ZIKV is cytotoxic and inhibits proliferation independent of different human origins, but inhibits neuronal differentiation and alters gene expression in a cell-strain-dependent manner.