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

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.