Growth of Zika virus in Brain Stem Cells Implies Involvement in Microcephaly

Experiments conducted in cultured human embryonic cortical neural progenitor cells (hNPCs) have demonstrated that these cells are readily infected by the Zika virus (ZIKV), which induces the cells to produce new Zika virus particles while disrupting normal cell metabolism in a fashion that eventually kills the cells.

Investigators at Johns Hopkins University (Baltimore, MD, USA) and colleagues at Florida State University (Tallahassee, USA) and Emory University (Atlanta, GA, USA) worked with hNPCs that had been derived from human induced pluripotent stem cells.

They reported in the March 4, 2016, online edition of the journal Cell Stem Cell that a strain of the ZIKV, MR766, serially passaged in monkey and mosquito cells efficiently infected hNPCs (more than 90% of cells were infected within three days). Infected hNPCs further released infectious ZIKV particles. ZIKV infection increased cell death and disrupted cell-cycle progression, resulting in attenuated hNPC growth.

Global gene expression analysis of infected hNPCs revealed transcriptional dysregulation, notably of cell-cycle-related pathways.

The results of this study point to hNPCs as being directly targeted by ZIKV. Furthermore, they describe an experimental model system to investigate the impact and mechanism of ZIKV on human brain development and provide a platform to screen therapeutic compounds.

“Studies of fetuses and babies with the telltale small brains and heads of microcephaly in Zika-affected areas have found abnormalities in the cortex, and Zika virus has been found in the fetal tissue,” said senior author Dr. Guo-li Ming, professor of neurology, neuroscience, psychiatry, and behavioral science at Johns Hopkins University. “While this study does not definitely prove that Zika virus causes microcephaly, it is very telling that the cells that form the cortex are potentially susceptible to the virus, and their growth could be disrupted by the virus.”

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